Cell-penetrating peptides(CPPs)hold great potential as a tool using non-invasive delivery of therapeutic or diagnostic molecules into mammalian cells,but their broad application has been limited by poor endosomal esca...Cell-penetrating peptides(CPPs)hold great potential as a tool using non-invasive delivery of therapeutic or diagnostic molecules into mammalian cells,but their broad application has been limited by poor endosomal escape.Thus,the rational design and selection of CPPs remains a challenge and calls for deeper mechanistic understandings.Here,we developed novel stapled cell-penetrating peptides based on the highly positively charged HIV Tat47-57 peptide using decafluorobiphenyl-cysteine SNAr chemistry which selectively disrupt endosomal membranes.A series of stapled peptides with a cross-linked structure were synthesized and investigated their cellular uptake,endosomal escape and intracellular delivery of cargoes.Among these peptides,analogues P3 and P6 demonstrated the highest cellular uptake and endosomal escape activities with efficiencies 3.5-9-fold higher than that of Tat47-57.Notably,the results demonstrated that the decafluorobiphenyl bridge of stapled peptides exhibited significant ability for cellular uptake and endosomal escape.Moreover,we found that fluorine atoms of decafluorobiphenyl bridge played a key role for disrupting endosomal membranes.Finally,the utility of this strategy has been demonstrated by the intracellular delivery of biomacromolecules(avidin and negatively charged phosphopeptides).Together,these results suggest that the decafluorobiphenyl-cysteine SNAr chemistry may be an efficient strategy for the development of novel stapled CPPs.展开更多
In this study,digested soybean protein(dspr)and peptides(dspe)were found to have different effects on the adhesion ability of Limosilactobacillus reuteri DSM17938 and HT-29 cells.Results found that dspr and dspe could...In this study,digested soybean protein(dspr)and peptides(dspe)were found to have different effects on the adhesion ability of Limosilactobacillus reuteri DSM17938 and HT-29 cells.Results found that dspr and dspe could increase L.reuteri adhesion ability by affecting their auto-aggregation and hydrophobicity during their stationary phase.The moonlighting protein may play a dominant role affected by dspe in the adhesion process of L.reuteri from stationary phase.Moreover,dspr and dspe also enhanced the adhesion ability of HT-29cells to L.reuteri DSM17938,and they might play different role at different stages of adhesion.dspr mainly promoted the expression of adhesion-related genes before L.reuteri adhesion.dspe increased them after the adhesion of L.reuteri from log phase and dspr mainly enhanced their expression after stationary phase L.reuteri adhesion.Soybean protein and peptides may therefore be considered as a potential effective modulator of L.reuteri adhesion to intestinal tract.展开更多
Oncolytic peptides have emerged as a distinct class of antitumor agents with the potential to overcome therapeutic resistance and enhance anticancer immunity.Most oncolytic peptides are naturally derived or structural...Oncolytic peptides have emerged as a distinct class of antitumor agents with the potential to overcome therapeutic resistance and enhance anticancer immunity.Most oncolytic peptides are naturally derived or structurally inspired by natural peptides,and typically display cationic and amphipathic features.Mechanistically,these physicochemical properties enable preferential binding to the negatively charged membranes of cancer cells and subsequent membrane disruption.Beyond direct membrane lysis,many naturally derived oncolytic peptides(NDOPs)perturb intracellular organelle membranes,trigger immunogenic cell death,and modulate immune cells and immune checkpoints,thereby amplifying the cancer-immunity cycle.Through these multifaceted mechanisms,NDOPs show a low tendency to induce drug resistance and can enhance response rates when combined with conventional therapies.Notably,four NDOP-based agents have advanced into clinical trials,underscoring their translational promise.In this review,we summarize the sources,structural features,and mechanisms of NDOPs,highlight innovative therapeutic applications and rational combination strategies,and further discuss the current clinical progress.We also outline key challenges and future directions for the development of NDOPs as next-generation anticancer therapeutics.展开更多
Classical structure–activity relationships(SAR)have limited predictive power for antimicrobial peptides(AMPs)because they assume fixed structures,single mechanisms,and independent physicochemical descriptors.In pract...Classical structure–activity relationships(SAR)have limited predictive power for antimicrobial peptides(AMPs)because they assume fixed structures,single mechanisms,and independent physicochemical descriptors.In practice,AMP activity arises from dynamic,multistate ensembles that reorganize with environment,concentration,and membrane context.Here,we propose that the AMP function is best described using an ensemble-based chemical framework grounded in free-energy landscapes and interfacial thermodynamics.Peptide sequences encode distributions of chemically accessible states rather than unique bioactive conformations,while environmental variables selectively redistribute these populations across interfacial,inserted,and oligomeric regimes.Biological outcomes such as membrane disruption,intracellular access,and selectivity emerge as conditional consequences of state population shifts rather than intrinsic sequence-encoded mechanisms.This perspective provides a chemically grounded alternative to static SAR and suggests that effective AMP design should focus on controlling ensemble redistribution under realistic interfacial environments.展开更多
The term“worm medicines”(Chong Yao)in Traditional Chinese Medicine encompasses a diverse category of small animal-derived therapeutics,including arthropods,amphibians,and reptiles,rather than strictly vermiform orga...The term“worm medicines”(Chong Yao)in Traditional Chinese Medicine encompasses a diverse category of small animal-derived therapeutics,including arthropods,amphibians,and reptiles,rather than strictly vermiform organisms.Many of these animals,such as scorpions,centipedes,toads,and horseflies,are toxic,and have been employed in clinical practice for centuries,despite limited understanding of their active compounds and underlying modes of action.Among the bioactive constituents extracted from these taxa,peptides represent a particularly promising class,with over 2000 identified to date.These peptides are primarily secreted from specialized exocrine glands,including venom,salivary,and cutaneous glands,and are characterized by high structural diversity and target specificity.Their potent modulatory effects on the nervous,cardiovascular,and immune systems make them excellent candidates for drug discovery and development.This review examines peptide-based compounds derived from the exocrine secretions of venomous and poisonous taxa historically employed in traditional Chinese“worm”medicines.Emphasis is placed on their biological origins,structural features,and pharmacological activities,highlighting their significant potential as a rich and largely untapped resource for modern therapeutic discovery.展开更多
Andrias davidianus bone peptides(ADBP),known for their potent xanthine oxidase(XOD)inhibitory activity,show promise as adjunctive agents for the treatment of hyperuricemia(HUA).However,their quality control and antihy...Andrias davidianus bone peptides(ADBP),known for their potent xanthine oxidase(XOD)inhibitory activity,show promise as adjunctive agents for the treatment of hyperuricemia(HUA).However,their quality control and antihyperuricemic efficacy across different farming regions have not been thoroughly investigated.This study undertook a comparative analysis of ADBP from nine representative farming locations,developed a high-performance liquid chromatography(HPLC)fingerprint,and evaluated the antihyperuricemic activity of the most promising sample both in vitro and in vivo.The nine ADBP samples predominantly consisted of low-molecular-weight peptides with high protein content.However,their mineral and amino acid profiles exhibited significant variability,which served as key distinguishing markers.A reliable HPLC fingerprint was established to characterize ADBP from the different farming regions.Based on compositional analysis and XOD inhibitory activity,the ADBP obtained from the Hunan Zhangjiajie(HNZJJ)region was selected for further investigation.In vitro experiments utilizing an optimized adenosine-induced HUA model in LO2 cells confirmed the uric acid-lowering effect of the selected ADBP.In vivo experiments using a mouse model demonstrated that ADBP significantly suppressed hepatic uric acid synthesis by inhibiting adenylate deaminase(ADA),XOD activity,and reducing serum uric acid levels.Additionally,ADBP alleviated HUAinduced liver damage by enhancing hepatic antioxidant defenses.Metabolomic analysis revealed that ADBPinduced alterations in liver metabolites may contribute to the alleviation of HUA.These metabolites were notably enriched in pathways related to linoleic acid metabolism,arginine and proline metabolism,caffeine metabolism,cysteine and methionine metabolism,and purine metabolism.These findings underscore the potential of ADBP as a functional ingredient for food and biomedical applications aimed at the prevention and adjunctive treatment of HUA.展开更多
With the intensified exploration of marine resources,marine bioactive peptides have become one of the research focuses in biomedicine,food science,and materials science because of their structural diversity,unique bio...With the intensified exploration of marine resources,marine bioactive peptides have become one of the research focuses in biomedicine,food science,and materials science because of their structural diversity,unique biological activities,and broad application potential.At present,the extraction of marine peptides has expanded beyond conventional chemical extraction and enzymatic hydrolysis,with microbial fermentation and gastrointestinal simulation technologies further broadening peptide diversity.In addition,the integration of multiple chromatographic techniques with advanced detectors has significantly improved the efficiency of marine peptide identification.Owing to their diverse biological activities,including immunoregulatory,antioxidant,antibacterial,antitumor,hypotensive,and hypoglycemic effects,marine peptides not only enrich the pool of candidates for marine drug development but also provide new perspectives for addressing numerous health challenges.Importantly,substantial progress has been made in the screening,identification,and mechanistic elucidation of marine bioactive peptides,driven by advances in high-throughput technologies and the bioinformatics.However,marine peptide research still faces several challenges,including complex sourcing,difficulties in large-scale acquisition,and insufficient exploration of biological activities.Therefore,this article concisely reviews recent progress in the extraction,purification,and identification of marine bioactive peptides,summarizes current research on their biological activities,and highlights the application of bioinformatics in marine peptide studies.展开更多
Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
Cancer is regarded as one of the leading causes of death worldwide,despite the progress of traditional therapies.Chemotherapy,radiotherapy,and surgery are often accompanied by significant side effects and the developm...Cancer is regarded as one of the leading causes of death worldwide,despite the progress of traditional therapies.Chemotherapy,radiotherapy,and surgery are often accompanied by significant side effects and the development of drug resistance contributes to making the fight against cancer even more challenging,which clearly highlights the urgent need to develop new therapeutic molecular approaches.In this context,natural peptides were introduced into the pharmaceutical market in the last decade and have replenished the ranks of effective anticancer agents due to their structural diversity,biocompatibility,and ability to selectively target tumor cells.Natural peptides play a dual role,directly inhibiting tumor growth and proliferation by inhibiting angiogenesis and,conversely,exhibiting an immunomodulatory effect by enhancing the activation of T lymphocytes and natural killer cells and positively altering the tumor microenvironment(TME).The aim of this work is to critically evaluate the available literature on the anticancer and immunomodulatory activities of natural peptides and their potential use,both as monotherapy and in combination therapy,with particular attention given to issues of stability,bioavailability,and scalability of production.As highlighted throughout this review,a promising area is the integration of natural peptides with their synthetic derivatives and combining them with modern approaches such as nanotechnology and personalized medicine,which opens new avenues in cancer treatment.展开更多
Postmenopausal estrogen deficiency predisposes women to atherosclerosis and cardiovascular pathologies.Edible dock protein-derived enzymatic hydrolysates(EDP),rich in ultra-short peptides,exhibit potential vascular pr...Postmenopausal estrogen deficiency predisposes women to atherosclerosis and cardiovascular pathologies.Edible dock protein-derived enzymatic hydrolysates(EDP),rich in ultra-short peptides,exhibit potential vascular protective properties,yet their efficacy in postmenopausal settings remains undefined.Utilizing an ovariectomized(OVX)rat model,we demonstrate that EDP,while not restoring estrogen/progesterone levels,significantly counteracted OVX-induced hyperlipidemia(reduced total cholesterol/low-density lipoprotein cholesterol,LDL-C)and rescued acetylcholine-mediated vasodilation in high-dose treatment(H-EDP).Singlecell transcriptomics of thoracoabdominal aortas revealed OVX-driven immune dysregulation:monocyte/macrophage expansion,T-cell depletion,disrupted Treg/Th17 equilibrium,and pro-inflammatory T cell receptor(TCR)uclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)activation.EDP rebalanced lymphoid populations(Treg/Th17 restoration),suppressed pro-inflammatory mediators,and enhanced antiinflammatory transforming growth factor-β(TGF-β)signaling.In myeloid compartments,EDP attenuated neutrophilia and monocytosis while inhibiting atherogenic metabolism.Endothelial analysis highlighted EDPenhanced lymphangiogenesis and immune-endothelial crosstalk via CXC chemokine ligand 12(CXCL12)/CXC chemokine receptor 4(CXCR4)axis.Smooth muscle cells exhibited EDP-mediated recovery of contractile SMC-Des populations,and modulation of leukocyte recruitment through vascular cell adhesion molecule-1(VCAM1)-Integrinα4β1 interactions.Fibroblast profiling showed EDP-induced expansion of Fibro-Barx1 subsets,restoring ECM homeostasis via Jag1-Notch2 pathways.Critically,EDP achieved these effects independent of estrogen restoration,establishing it as a hormone-independent therapeutic strategy to mitigate vascular dysfunction and immune-metabolic dysregulation in estrogen-deficient states.展开更多
Although previous IRMPD(infrared multiple photon dissociation)experi-ments proposed the presence of proto-nation of the C=O peptide bond in certain tripeptides with lower energy than traditional amino protonation,subs...Although previous IRMPD(infrared multiple photon dissociation)experi-ments proposed the presence of proto-nation of the C=O peptide bond in certain tripeptides with lower energy than traditional amino protonation,subsequent theoretical calculations have revealed that their conclusions are unreliable.Therefore,it has become imperative to ex-plore the existence of such molecules.In this study,based on reasonable speculation,four dipeptides and four tripeptides were selected and their protonated configurations were sys-tematically searched.High-level theoretical calculations using the composite CBS-QB3 method indicated that at least two dipeptides,GP and GV(G:glycine,P:proline,V:valine),have been identified as the candidate molecules with protonation at the amide oxygen as the global minimum.GP is also identified as the smallest dipeptide with the cis-peptide confor-mation as the global minimum.The electrostatic potentials and the transition states between the two protonated forms have been calculated to uncover the determining mechanism for the predominance of peptide bond protonation.In addition,the chemical(infrared,IR)and elec-tronic(X-ray photoelectronic spectroscopy and near-edge X-ray absorption fine structures,XPS and NEXAFS)structural calculations were performed to distinguish between these dif-ferent protonated forms in future experiments.This study provides valuable insights into the competitive coexistence between the two protonated forms of short peptides and deepens our understanding of the protonation process in the early stage of protein synthesis.展开更多
Bioactive peptides have emerged as powerful functional ingredients in cosmetics,valued for their rapid action,high specificity,and low toxicity.These short amino acid sequences can deliver antimicrobial,antioxidant,an...Bioactive peptides have emerged as powerful functional ingredients in cosmetics,valued for their rapid action,high specificity,and low toxicity.These short amino acid sequences can deliver antimicrobial,antioxidant,anti-aging,UVprotective,and skin-brightening effects by selectively interacting with biological targets in the skin.This review offers a comprehensive synthesis of recent advances in the field,from peptide classification and skin-related mechanisms of action to production methods and discovery technologies.Key peptide classes are outlined by their functions and pathways,followed by a comparative analysis of current production routes—chemical synthesis,enzymatic protein hydrolysis,and recombinant biosynthesis via synthetic biology—highlighting each approach’s advantages,limitations,and scalability for cosmetic use.Strategies to enhance peptide stability and delivery are discussed,including chemical modifications(e.g.,acetylation,lipidation,and cyclization)that improve resistance to degradation and innovative formulation approaches(such as liposomes,nanoparticles,and other carriers)that facilitate effective skin penetration.Furthermore,high-throughput discovery platforms,including phage display libraries and artificial intelligence(AI)-driven computational design(e.g.,machine learning and deep learning),are dramatically improving the efficiency and precision of identifying and optimizing new bioactive peptides.Enabled by these technological innovations,the field is rapidly evolving:synthetic biology and bioinformatics now allow large-scale peptide biosynthesis and rational design of multifunctional peptides.Continued progress in production,stabilization,and AI-guided design is expected to overcome current challenges and fully unlock the potential of bioactive peptides in next-generation cosmetic formulations.展开更多
This study utilized peptidomics and bioinformatics to investigate the structure-hypocholesterolemic activity relationships of oyster peptides(OPs).Ion-exchange chromatography separated OP into three fractions(OP-1,OP-...This study utilized peptidomics and bioinformatics to investigate the structure-hypocholesterolemic activity relationships of oyster peptides(OPs).Ion-exchange chromatography separated OP into three fractions(OP-1,OP-2,and OP-3).OP-2 showed the strongest inhibitory effect on pancreatic lipase(PL)(76.16%)and cholesterol esterase(CE)(66.43%),reducing total cholesterol(TC)in a concentration-dependent manner.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that active peptides(<3 kDa)were rich in hydrophobic(Leu,Ala)and acidic(Asp,Glu)residues.Bioinformatics and molecular docking identified key peptides(LPFQ,LNFP)with dual-enzyme inhibitory activity.Furthermore,LNFP demonstrated a significant cholesterol-lowering effect in a HepG2 cell model(seeded at 5.0×105 cells/well in six-well plates)by reducing intracellular cholesterol accumulation and enhancing low-density lipoprotein(LDL)uptake.At 50μmol/L,its cholesterol lowering effect was similar to that of simvastatin at 10μmol/L.These findings highlight the structural motifs crucial for dual-enzyme inhibition and hepatic cholesterol regulation,emphasizing the potential of OPs as a natural cholesterol-lowering agent and promising candidate for future therapeutic development.Further studies on their gastrointestinal stability and in vivo efficacy are warranted to fully assess their potential for dietary intervention.展开更多
Ganoderma sinense is a traditional and protein-rich edible fungus with outstanding immunoregulatory activity.However,the mechanism through which G.sinense protein hydrolysates and peptides exert their immunomodulatory...Ganoderma sinense is a traditional and protein-rich edible fungus with outstanding immunoregulatory activity.However,the mechanism through which G.sinense protein hydrolysates and peptides exert their immunomodulatory effects is unclear.The objective of this study was to prepare and isolate immunologically active peptides from G.sinense protein hydrolysates(GSP) and to investigate their impact on the activation of macrophages.G.sinense peptides with low molecular weights(< 1 kDa,87.76%) markedly promoted RAW264.7 cell proliferation;increased their phagocytic capacity,nitric oxide(NO),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),and IL-6 secretion and reactive oxygen species(ROS) production;and upregulated Tlr2 mRNA expression.In addition,GSP promoted nuclear factor kappa-B(NF-κB) activation and translocation through the upregulation of p65 and p-p65 protein expression.Virtual molecular screening technology revealed that compared with other peptides,the SFAGNIPVNR,YGDAFIR and TVSYLPAPQR peptides derived from GSP showed stronger binding affinities.Interaction site map analysis indicated that the SFAGNIPVNR and YGDAFIR peptides formed stable hydrogen bonds with toll-like receptor 2(TLR2).Together,these results suggested that G.sinense peptides can serve as important ingredients in nutraceuticals or functional foods.展开更多
Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face wit...Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed C–H activation has been employed for the functionalization of amino acids and peptides.Through domino C–H activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed C–H activation/annulation.展开更多
Backgrounds:Autocrine motility factor(AMF)represents a paradoxical protein with dual roles in cancer progression and therapy.This study investigated AMF-derived tetradecapeptides as novel chemosensitizing agents to ov...Backgrounds:Autocrine motility factor(AMF)represents a paradoxical protein with dual roles in cancer progression and therapy.This study investigated AMF-derived tetradecapeptides as novel chemosensitizing agents to overcome multidrug resistance(MDR)in hematological malignancies(HMs).Methods:Seven AMF variants were screened for anticancer activity across 14 human cancer cell lines using MTT and Cell Counting Kit-8(CCK-8)assays.Four tetradecapeptides(AMF-derived peptides AAP,HGP,HTP,and SKP)corresponding to the AMF206-219 region were designed and evaluated in three HM cell lines(HL-60,CCRF-CEM,IM-9)for growth inhibition,cellular internalization,reactive oxygen species(ROS)production,mitochondrial membrane potential,and gene/protein expression.Synergism with doxorubicin(DOX)and other chemotherapeutic agents was quantified by combination index(CI)analysis using the Chou-Talalay method and spheroid culture assays.Results:AMF variants demonstrated broad-spectrum anticancer activity,with HL-60 acute promyelocytic leukemia cells showing exceptional sensitivity.AMF variants functioned as cell competition-mediated killing signals,converting cancer cells into metabolically compromised“loser”cells through glucose metabolism disruption and oxidative stress induction.Among the four tetradecapeptides,AAP exhibited the most consistent growth inhibition across HM cell lines(HL-60,CCRF-CEM,IM-9)while maintaining gp78/AMFR-mediated cellular internalization.AAP treatment induced dose-dependent ROS production,mitochondrial membrane potential alterations,and p53 upregulation,though glucose-6-phosphate dehydrogenase(G6PD)suppression showed cell-type specificity.Remarkably,AAP demonstrated potent synergistic effects with DOX,reducing IC50 values by 28–53%across tested HM cells through multiple complementary mechanisms:enhanced intracellular DOX retention,elevated oxidative stress,and downregulation of multidrug resistance protein 1(MDR1;P-glycoprotein)and multidrug resistance-associated protein 1(MRP1)in specific cell types.AAP similarly synergized with daunorubicin but not with etoposide or cytarabine,suggesting selectivity for ROS-inducing anthracyclines.Conclusions:These findings establish AMF-derived peptides as promising human-origin chemosensitizers capable of overcoming multidrug resistance in HMs through multi-targeted mechanisms.The ability to reduce anthracycline dosing while maintaining efficacy offers potential for minimizing cardiotoxicity and other dose-limiting adverse effects,warranting further preclinical development toward clinical translation.展开更多
A 15 peptide with anti-aging effects was prepared by solid-phase synthesis through computer-aided simulation design.Based on the amphiphilicity of peptides,polymer nanomicelles can be formed through supramolecular sel...A 15 peptide with anti-aging effects was prepared by solid-phase synthesis through computer-aided simulation design.Based on the amphiphilicity of peptides,polymer nanomicelles can be formed through supramolecular self-assembly in solution,and the structural morphology is characterized by transmission electron microscopy as a nano spherical structure.defined as ball peptide.Compared with traditional linear peptides,the skin permeability of peptide within 2 h increased by 150%,and the anti enzymatic ability within 90 min increased by 156.8%.The efficacy verification experiments based on cell level showed that spherical nano peptides exhibited significant anti-aging effects.At the same time,it can be used as a delivery carrier to load other active molecules for transdermal absorption,and can be applied as a new type of peptide raw material in cosmetic products and formulations.展开更多
CLAVATA3/EMBRYO SURROUNDING REGION(CLE)peptides are among the most well-studied families of plant peptide hormones,playing essential roles in regulating a wide range of biological processes,including plant growth,deve...CLAVATA3/EMBRYO SURROUNDING REGION(CLE)peptides are among the most well-studied families of plant peptide hormones,playing essential roles in regulating a wide range of biological processes,including plant growth,development,and stress adaptation.In this review,we explore the structural diversity of CLE peptides across species and provide a comprehensive summary of the biological functions and signaling mechanisms of CLE peptides.We first discuss their roles in plant development,including stem cell homeostasis,meristem activity,vascular patterning,and reproductive organ formation.We then explore how CLE peptides contribute to plant responses to environmental stresses such as nutrient deficiency,drought,and heat.Additionally,we summarize recent insights into the crosstalk between CLE signaling and classical phytohormonal pathways.Finally,we outline current challenges and propose future directions.By integrating knowledge from developmental and stress biology,this review aims to promote a deeper understanding of CLE signaling in dynamic plant environments,leveraging this knowledge to enhance crop resilience and productivity in changing climates.展开更多
Background The overuse of antibiotics in both veterinary and human medicine has resulted in the emergence of antibiotic-resistant bacteria,prompting a search for effective alternatives.Antimicrobial peptides(AMPs)are ...Background The overuse of antibiotics in both veterinary and human medicine has resulted in the emergence of antibiotic-resistant bacteria,prompting a search for effective alternatives.Antimicrobial peptides(AMPs)are short,often cationic,peptide-based molecules with antimicrobial and immunomodulatory activity,which makes them promising alternatives to conventional antibiotics in poultry production.Results From a prior machine-learning-guided screen of 875 candidate AMPs against a wide bacterial panel,62exhibited activity against avian pathogenic Escherichia coli(APEC)and low in vitro hemolytic and cytotoxic activity.We selected three lead AMPs from this list(named TeRu4,TeBi1,and PeNi4),and evaluated their in vitro and in vivo efficacy,safety,and immunomodulatory potential for use in poultry farming.In animal experiments,AMPs were administered via in ovo injection on d 18 of embryonic development.In APEC challenge trials,yolk sacs were inoculated with APEC post-hatch to assess early chick mortality,while in pen trials,birds were raised in a commercial production setting for 35 d.For challenged birds,TeBi1(10μg/egg)significantly reduced culture-positive rates for APEC in the air sac and pericardium,increased body weight by 50%and reduced cytokine transcript levels by 10%-30%on d 7post hatch.In HD11 chicken macrophage-like cultured cells,TeRu4(16μg/mL)suppressed lipopolysaccharide(LPS)-induced pro-inflammatory cytokine transcript levels.In pen trials,TeRu4(20μg/egg)increased the survival probability of female birds by 4.9%,while TeBi1(20μg/egg)increased the survival probability of all birds by 4.4%,by d 35.Gene expression analysis revealed AMP-and sex-specific cytokine responses.In pen trials,no significant differences were observed in mean weights,feed conversion ratio(FCR),and flock uniformity on d 35.By integrating high-throughput in ovo automation with large-scale commercial pen trials,this study provides a systematic translational bridge from in silico AI discovery to field-relevant poultry production interventions.Conclusions These findings demonstrate that TeBi1 and TeRu4 are promising antibiotic alternatives that improve survival,modulate immune responses,and maintain normal growth performance in broiler chickens in this experimental setting.展开更多
Nitrile oxide is a highly reactive species used for organic synthesis and bioconjugation.Herein,we developed a novel approach for disulfide formation and capping of N-terminal cysteine in peptides mediated by bromo ni...Nitrile oxide is a highly reactive species used for organic synthesis and bioconjugation.Herein,we developed a novel approach for disulfide formation and capping of N-terminal cysteine in peptides mediated by bromo nitrile oxide.1,1-Dibromoformaldoxime acts as the precursor for bromo nitrile oxide.This transformation proceeds under mild conditions with rapid kinetics,efficiently converting a broad range of thiophenols,thiols,and cysteine-containing native peptides into disulfides,cyclic disulfides,or thiazolidin-2-one oximes.Notably,oxidant-sensitive residues such as methionine,tyrosine,and tryptophan are well tolerated without over-oxidation.The compatibility with aqueous media further highlights its potential for the late-stage modification of native peptides and the derivatization of biologically active molecules.展开更多
基金supported by the grants from the National Natural Science Foundation of China(No.82404426)the Natural Science Foundation of Gansu Province(No.18JR3RA280)+2 种基金the Funds for Fundamental Research Creative Groups of Gansu Province(No.20JR5RA310)Shihezi University High-level Talent Research Startup funds(No.RCZK202446)Tianchi Talent Introduction Plan。
摘要Cell-penetrating peptides(CPPs)hold great potential as a tool using non-invasive delivery of therapeutic or diagnostic molecules into mammalian cells,but their broad application has been limited by poor endosomal escape.Thus,the rational design and selection of CPPs remains a challenge and calls for deeper mechanistic understandings.Here,we developed novel stapled cell-penetrating peptides based on the highly positively charged HIV Tat47-57 peptide using decafluorobiphenyl-cysteine SNAr chemistry which selectively disrupt endosomal membranes.A series of stapled peptides with a cross-linked structure were synthesized and investigated their cellular uptake,endosomal escape and intracellular delivery of cargoes.Among these peptides,analogues P3 and P6 demonstrated the highest cellular uptake and endosomal escape activities with efficiencies 3.5-9-fold higher than that of Tat47-57.Notably,the results demonstrated that the decafluorobiphenyl bridge of stapled peptides exhibited significant ability for cellular uptake and endosomal escape.Moreover,we found that fluorine atoms of decafluorobiphenyl bridge played a key role for disrupting endosomal membranes.Finally,the utility of this strategy has been demonstrated by the intracellular delivery of biomacromolecules(avidin and negatively charged phosphopeptides).Together,these results suggest that the decafluorobiphenyl-cysteine SNAr chemistry may be an efficient strategy for the development of novel stapled CPPs.
基金supported by the National Key Research and Development Program of China(2021YFD2100402)the fund of Cultivation Project of Double First-Class Disciplines of Food Science and Engineering,Beijing Technology&Business University(BTBUYXTD202207).
摘要In this study,digested soybean protein(dspr)and peptides(dspe)were found to have different effects on the adhesion ability of Limosilactobacillus reuteri DSM17938 and HT-29 cells.Results found that dspr and dspe could increase L.reuteri adhesion ability by affecting their auto-aggregation and hydrophobicity during their stationary phase.The moonlighting protein may play a dominant role affected by dspe in the adhesion process of L.reuteri from stationary phase.Moreover,dspr and dspe also enhanced the adhesion ability of HT-29cells to L.reuteri DSM17938,and they might play different role at different stages of adhesion.dspr mainly promoted the expression of adhesion-related genes before L.reuteri adhesion.dspe increased them after the adhesion of L.reuteri from log phase and dspr mainly enhanced their expression after stationary phase L.reuteri adhesion.Soybean protein and peptides may therefore be considered as a potential effective modulator of L.reuteri adhesion to intestinal tract.
基金supported by State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine(Nos.SHUTCM-SKL-202520,GMUSKL-202501)Three-year Action Plan for Shanghai TCM Development and Inheritance Program[No.ZY(2025-2027)-2-2-1]+2 种基金CACMS Innovation Fund(No.CI2023C034LH)High level Key Discipline of National Administration of Traditional Chinese Medicine(No.zyyzdxk-2023071)East China Normal University-Shanghai Putuo District Central Hospital Collaborative Research Center for Translational Medicine(No.ECNU-SPDH CCTM-202504)。
摘要Oncolytic peptides have emerged as a distinct class of antitumor agents with the potential to overcome therapeutic resistance and enhance anticancer immunity.Most oncolytic peptides are naturally derived or structurally inspired by natural peptides,and typically display cationic and amphipathic features.Mechanistically,these physicochemical properties enable preferential binding to the negatively charged membranes of cancer cells and subsequent membrane disruption.Beyond direct membrane lysis,many naturally derived oncolytic peptides(NDOPs)perturb intracellular organelle membranes,trigger immunogenic cell death,and modulate immune cells and immune checkpoints,thereby amplifying the cancer-immunity cycle.Through these multifaceted mechanisms,NDOPs show a low tendency to induce drug resistance and can enhance response rates when combined with conventional therapies.Notably,four NDOP-based agents have advanced into clinical trials,underscoring their translational promise.In this review,we summarize the sources,structural features,and mechanisms of NDOPs,highlight innovative therapeutic applications and rational combination strategies,and further discuss the current clinical progress.We also outline key challenges and future directions for the development of NDOPs as next-generation anticancer therapeutics.
摘要Classical structure–activity relationships(SAR)have limited predictive power for antimicrobial peptides(AMPs)because they assume fixed structures,single mechanisms,and independent physicochemical descriptors.In practice,AMP activity arises from dynamic,multistate ensembles that reorganize with environment,concentration,and membrane context.Here,we propose that the AMP function is best described using an ensemble-based chemical framework grounded in free-energy landscapes and interfacial thermodynamics.Peptide sequences encode distributions of chemically accessible states rather than unique bioactive conformations,while environmental variables selectively redistribute these populations across interfacial,inserted,and oligomeric regimes.Biological outcomes such as membrane disruption,intracellular access,and selectivity emerge as conditional consequences of state population shifts rather than intrinsic sequence-encoded mechanisms.This perspective provides a chemically grounded alternative to static SAR and suggests that effective AMP design should focus on controlling ensemble redistribution under realistic interfacial environments.
基金supported by the Key Research and Development Program of Guangzhou Science and Technology Plan Project(2024B03J0011)National Natural Science Foundation of China(32522015,32570586,32370538)+1 种基金National Key Research and Development Program of China(2023YFF1304900)Yunnan Province Grant(2021000097,202402AA310010,202403AC100010)。
摘要The term“worm medicines”(Chong Yao)in Traditional Chinese Medicine encompasses a diverse category of small animal-derived therapeutics,including arthropods,amphibians,and reptiles,rather than strictly vermiform organisms.Many of these animals,such as scorpions,centipedes,toads,and horseflies,are toxic,and have been employed in clinical practice for centuries,despite limited understanding of their active compounds and underlying modes of action.Among the bioactive constituents extracted from these taxa,peptides represent a particularly promising class,with over 2000 identified to date.These peptides are primarily secreted from specialized exocrine glands,including venom,salivary,and cutaneous glands,and are characterized by high structural diversity and target specificity.Their potent modulatory effects on the nervous,cardiovascular,and immune systems make them excellent candidates for drug discovery and development.This review examines peptide-based compounds derived from the exocrine secretions of venomous and poisonous taxa historically employed in traditional Chinese“worm”medicines.Emphasis is placed on their biological origins,structural features,and pharmacological activities,highlighting their significant potential as a rich and largely untapped resource for modern therapeutic discovery.
基金supported by the Shenzhen Science and Technology Program(JCYJ20240813112052067)the Haday Visionary Science Advancement Fund.
摘要Andrias davidianus bone peptides(ADBP),known for their potent xanthine oxidase(XOD)inhibitory activity,show promise as adjunctive agents for the treatment of hyperuricemia(HUA).However,their quality control and antihyperuricemic efficacy across different farming regions have not been thoroughly investigated.This study undertook a comparative analysis of ADBP from nine representative farming locations,developed a high-performance liquid chromatography(HPLC)fingerprint,and evaluated the antihyperuricemic activity of the most promising sample both in vitro and in vivo.The nine ADBP samples predominantly consisted of low-molecular-weight peptides with high protein content.However,their mineral and amino acid profiles exhibited significant variability,which served as key distinguishing markers.A reliable HPLC fingerprint was established to characterize ADBP from the different farming regions.Based on compositional analysis and XOD inhibitory activity,the ADBP obtained from the Hunan Zhangjiajie(HNZJJ)region was selected for further investigation.In vitro experiments utilizing an optimized adenosine-induced HUA model in LO2 cells confirmed the uric acid-lowering effect of the selected ADBP.In vivo experiments using a mouse model demonstrated that ADBP significantly suppressed hepatic uric acid synthesis by inhibiting adenylate deaminase(ADA),XOD activity,and reducing serum uric acid levels.Additionally,ADBP alleviated HUAinduced liver damage by enhancing hepatic antioxidant defenses.Metabolomic analysis revealed that ADBPinduced alterations in liver metabolites may contribute to the alleviation of HUA.These metabolites were notably enriched in pathways related to linoleic acid metabolism,arginine and proline metabolism,caffeine metabolism,cysteine and methionine metabolism,and purine metabolism.These findings underscore the potential of ADBP as a functional ingredient for food and biomedical applications aimed at the prevention and adjunctive treatment of HUA.
基金supported by the National Key Research and Development Program of China(No.2023YFC2812500).
摘要With the intensified exploration of marine resources,marine bioactive peptides have become one of the research focuses in biomedicine,food science,and materials science because of their structural diversity,unique biological activities,and broad application potential.At present,the extraction of marine peptides has expanded beyond conventional chemical extraction and enzymatic hydrolysis,with microbial fermentation and gastrointestinal simulation technologies further broadening peptide diversity.In addition,the integration of multiple chromatographic techniques with advanced detectors has significantly improved the efficiency of marine peptide identification.Owing to their diverse biological activities,including immunoregulatory,antioxidant,antibacterial,antitumor,hypotensive,and hypoglycemic effects,marine peptides not only enrich the pool of candidates for marine drug development but also provide new perspectives for addressing numerous health challenges.Importantly,substantial progress has been made in the screening,identification,and mechanistic elucidation of marine bioactive peptides,driven by advances in high-throughput technologies and the bioinformatics.However,marine peptide research still faces several challenges,including complex sourcing,difficulties in large-scale acquisition,and insufficient exploration of biological activities.Therefore,this article concisely reviews recent progress in the extraction,purification,and identification of marine bioactive peptides,summarizes current research on their biological activities,and highlights the application of bioinformatics in marine peptide studies.
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
摘要Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
基金supported by the Higher Education and Science Committee of MESCS RA(Research project No.24RL-1D014).
摘要Cancer is regarded as one of the leading causes of death worldwide,despite the progress of traditional therapies.Chemotherapy,radiotherapy,and surgery are often accompanied by significant side effects and the development of drug resistance contributes to making the fight against cancer even more challenging,which clearly highlights the urgent need to develop new therapeutic molecular approaches.In this context,natural peptides were introduced into the pharmaceutical market in the last decade and have replenished the ranks of effective anticancer agents due to their structural diversity,biocompatibility,and ability to selectively target tumor cells.Natural peptides play a dual role,directly inhibiting tumor growth and proliferation by inhibiting angiogenesis and,conversely,exhibiting an immunomodulatory effect by enhancing the activation of T lymphocytes and natural killer cells and positively altering the tumor microenvironment(TME).The aim of this work is to critically evaluate the available literature on the anticancer and immunomodulatory activities of natural peptides and their potential use,both as monotherapy and in combination therapy,with particular attention given to issues of stability,bioavailability,and scalability of production.As highlighted throughout this review,a promising area is the integration of natural peptides with their synthetic derivatives and combining them with modern approaches such as nanotechnology and personalized medicine,which opens new avenues in cancer treatment.
基金supported by grants from National High Level Hospital Clinical Research Funding(BJ-2024-219)National Key Research and Development Program of China(2023YFF1104400)+2 种基金National Natural Science Foundation of China(82271597)National High Level Hospital Clinical Research Funding(BJ-2023-123)Beijing Municipal Natural Science Foundation(7242120)。
摘要Postmenopausal estrogen deficiency predisposes women to atherosclerosis and cardiovascular pathologies.Edible dock protein-derived enzymatic hydrolysates(EDP),rich in ultra-short peptides,exhibit potential vascular protective properties,yet their efficacy in postmenopausal settings remains undefined.Utilizing an ovariectomized(OVX)rat model,we demonstrate that EDP,while not restoring estrogen/progesterone levels,significantly counteracted OVX-induced hyperlipidemia(reduced total cholesterol/low-density lipoprotein cholesterol,LDL-C)and rescued acetylcholine-mediated vasodilation in high-dose treatment(H-EDP).Singlecell transcriptomics of thoracoabdominal aortas revealed OVX-driven immune dysregulation:monocyte/macrophage expansion,T-cell depletion,disrupted Treg/Th17 equilibrium,and pro-inflammatory T cell receptor(TCR)uclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)activation.EDP rebalanced lymphoid populations(Treg/Th17 restoration),suppressed pro-inflammatory mediators,and enhanced antiinflammatory transforming growth factor-β(TGF-β)signaling.In myeloid compartments,EDP attenuated neutrophilia and monocytosis while inhibiting atherogenic metabolism.Endothelial analysis highlighted EDPenhanced lymphangiogenesis and immune-endothelial crosstalk via CXC chemokine ligand 12(CXCL12)/CXC chemokine receptor 4(CXCR4)axis.Smooth muscle cells exhibited EDP-mediated recovery of contractile SMC-Des populations,and modulation of leukocyte recruitment through vascular cell adhesion molecule-1(VCAM1)-Integrinα4β1 interactions.Fibroblast profiling showed EDP-induced expansion of Fibro-Barx1 subsets,restoring ECM homeostasis via Jag1-Notch2 pathways.Critically,EDP achieved these effects independent of estrogen restoration,establishing it as a hormone-independent therapeutic strategy to mitigate vascular dysfunction and immune-metabolic dysregulation in estrogen-deficient states.
基金supported by the Excellent Research and Innovation Team Project of Anhui Province (2022AH010001)。
摘要Although previous IRMPD(infrared multiple photon dissociation)experi-ments proposed the presence of proto-nation of the C=O peptide bond in certain tripeptides with lower energy than traditional amino protonation,subsequent theoretical calculations have revealed that their conclusions are unreliable.Therefore,it has become imperative to ex-plore the existence of such molecules.In this study,based on reasonable speculation,four dipeptides and four tripeptides were selected and their protonated configurations were sys-tematically searched.High-level theoretical calculations using the composite CBS-QB3 method indicated that at least two dipeptides,GP and GV(G:glycine,P:proline,V:valine),have been identified as the candidate molecules with protonation at the amide oxygen as the global minimum.GP is also identified as the smallest dipeptide with the cis-peptide confor-mation as the global minimum.The electrostatic potentials and the transition states between the two protonated forms have been calculated to uncover the determining mechanism for the predominance of peptide bond protonation.In addition,the chemical(infrared,IR)and elec-tronic(X-ray photoelectronic spectroscopy and near-edge X-ray absorption fine structures,XPS and NEXAFS)structural calculations were performed to distinguish between these dif-ferent protonated forms in future experiments.This study provides valuable insights into the competitive coexistence between the two protonated forms of short peptides and deepens our understanding of the protonation process in the early stage of protein synthesis.
基金financially supported by the National Key Research and Development Program of China(2024YFF1106300)the National Natural Science Foundation of China(U24A20368,32370066)the Jiangsu Basic Research Center for Synthetic Biology(BK20233003).
摘要Bioactive peptides have emerged as powerful functional ingredients in cosmetics,valued for their rapid action,high specificity,and low toxicity.These short amino acid sequences can deliver antimicrobial,antioxidant,anti-aging,UVprotective,and skin-brightening effects by selectively interacting with biological targets in the skin.This review offers a comprehensive synthesis of recent advances in the field,from peptide classification and skin-related mechanisms of action to production methods and discovery technologies.Key peptide classes are outlined by their functions and pathways,followed by a comparative analysis of current production routes—chemical synthesis,enzymatic protein hydrolysis,and recombinant biosynthesis via synthetic biology—highlighting each approach’s advantages,limitations,and scalability for cosmetic use.Strategies to enhance peptide stability and delivery are discussed,including chemical modifications(e.g.,acetylation,lipidation,and cyclization)that improve resistance to degradation and innovative formulation approaches(such as liposomes,nanoparticles,and other carriers)that facilitate effective skin penetration.Furthermore,high-throughput discovery platforms,including phage display libraries and artificial intelligence(AI)-driven computational design(e.g.,machine learning and deep learning),are dramatically improving the efficiency and precision of identifying and optimizing new bioactive peptides.Enabled by these technological innovations,the field is rapidly evolving:synthetic biology and bioinformatics now allow large-scale peptide biosynthesis and rational design of multifunctional peptides.Continued progress in production,stabilization,and AI-guided design is expected to overcome current challenges and fully unlock the potential of bioactive peptides in next-generation cosmetic formulations.
摘要This study utilized peptidomics and bioinformatics to investigate the structure-hypocholesterolemic activity relationships of oyster peptides(OPs).Ion-exchange chromatography separated OP into three fractions(OP-1,OP-2,and OP-3).OP-2 showed the strongest inhibitory effect on pancreatic lipase(PL)(76.16%)and cholesterol esterase(CE)(66.43%),reducing total cholesterol(TC)in a concentration-dependent manner.Analysis by liquid chromatography-mass spectrometry(LC-MS)indicated that active peptides(<3 kDa)were rich in hydrophobic(Leu,Ala)and acidic(Asp,Glu)residues.Bioinformatics and molecular docking identified key peptides(LPFQ,LNFP)with dual-enzyme inhibitory activity.Furthermore,LNFP demonstrated a significant cholesterol-lowering effect in a HepG2 cell model(seeded at 5.0×105 cells/well in six-well plates)by reducing intracellular cholesterol accumulation and enhancing low-density lipoprotein(LDL)uptake.At 50μmol/L,its cholesterol lowering effect was similar to that of simvastatin at 10μmol/L.These findings highlight the structural motifs crucial for dual-enzyme inhibition and hepatic cholesterol regulation,emphasizing the potential of OPs as a natural cholesterol-lowering agent and promising candidate for future therapeutic development.Further studies on their gastrointestinal stability and in vivo efficacy are warranted to fully assess their potential for dietary intervention.
基金supported by the National Natural Science Foundation,China(32402067)the Startup Fund for Scientific Research,Fujian Medical University(XRCZX2020032)the Natural Science Foundation of Fujian Province,China(2023J01307)。
摘要Ganoderma sinense is a traditional and protein-rich edible fungus with outstanding immunoregulatory activity.However,the mechanism through which G.sinense protein hydrolysates and peptides exert their immunomodulatory effects is unclear.The objective of this study was to prepare and isolate immunologically active peptides from G.sinense protein hydrolysates(GSP) and to investigate their impact on the activation of macrophages.G.sinense peptides with low molecular weights(< 1 kDa,87.76%) markedly promoted RAW264.7 cell proliferation;increased their phagocytic capacity,nitric oxide(NO),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),and IL-6 secretion and reactive oxygen species(ROS) production;and upregulated Tlr2 mRNA expression.In addition,GSP promoted nuclear factor kappa-B(NF-κB) activation and translocation through the upregulation of p65 and p-p65 protein expression.Virtual molecular screening technology revealed that compared with other peptides,the SFAGNIPVNR,YGDAFIR and TVSYLPAPQR peptides derived from GSP showed stronger binding affinities.Interaction site map analysis indicated that the SFAGNIPVNR and YGDAFIR peptides formed stable hydrogen bonds with toll-like receptor 2(TLR2).Together,these results suggested that G.sinense peptides can serve as important ingredients in nutraceuticals or functional foods.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20220409)the National Natural Science Foundation of China(No.22401153)+2 种基金the FWO[Fund for Scientific Research-Flanders(Belgium)]for financial support(recipient Erik V.Van der Eycken)the Research Council of the KU Leuven(recipient Erik V.Van der Eycken)the support of the"RUDN University Strategic Academic Leadership Program"(recipient Erik V.Van der Eycken).
摘要Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed C–H activation has been employed for the functionalization of amino acids and peptides.Through domino C–H activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed C–H activation/annulation.
基金supported by the National Research Foundation of Korea(NRF)Grant funded by the Korea Government(MSIT)(2022R1I1A1A01063465).
摘要Backgrounds:Autocrine motility factor(AMF)represents a paradoxical protein with dual roles in cancer progression and therapy.This study investigated AMF-derived tetradecapeptides as novel chemosensitizing agents to overcome multidrug resistance(MDR)in hematological malignancies(HMs).Methods:Seven AMF variants were screened for anticancer activity across 14 human cancer cell lines using MTT and Cell Counting Kit-8(CCK-8)assays.Four tetradecapeptides(AMF-derived peptides AAP,HGP,HTP,and SKP)corresponding to the AMF206-219 region were designed and evaluated in three HM cell lines(HL-60,CCRF-CEM,IM-9)for growth inhibition,cellular internalization,reactive oxygen species(ROS)production,mitochondrial membrane potential,and gene/protein expression.Synergism with doxorubicin(DOX)and other chemotherapeutic agents was quantified by combination index(CI)analysis using the Chou-Talalay method and spheroid culture assays.Results:AMF variants demonstrated broad-spectrum anticancer activity,with HL-60 acute promyelocytic leukemia cells showing exceptional sensitivity.AMF variants functioned as cell competition-mediated killing signals,converting cancer cells into metabolically compromised“loser”cells through glucose metabolism disruption and oxidative stress induction.Among the four tetradecapeptides,AAP exhibited the most consistent growth inhibition across HM cell lines(HL-60,CCRF-CEM,IM-9)while maintaining gp78/AMFR-mediated cellular internalization.AAP treatment induced dose-dependent ROS production,mitochondrial membrane potential alterations,and p53 upregulation,though glucose-6-phosphate dehydrogenase(G6PD)suppression showed cell-type specificity.Remarkably,AAP demonstrated potent synergistic effects with DOX,reducing IC50 values by 28–53%across tested HM cells through multiple complementary mechanisms:enhanced intracellular DOX retention,elevated oxidative stress,and downregulation of multidrug resistance protein 1(MDR1;P-glycoprotein)and multidrug resistance-associated protein 1(MRP1)in specific cell types.AAP similarly synergized with daunorubicin but not with etoposide or cytarabine,suggesting selectivity for ROS-inducing anthracyclines.Conclusions:These findings establish AMF-derived peptides as promising human-origin chemosensitizers capable of overcoming multidrug resistance in HMs through multi-targeted mechanisms.The ability to reduce anthracycline dosing while maintaining efficacy offers potential for minimizing cardiotoxicity and other dose-limiting adverse effects,warranting further preclinical development toward clinical translation.
摘要A 15 peptide with anti-aging effects was prepared by solid-phase synthesis through computer-aided simulation design.Based on the amphiphilicity of peptides,polymer nanomicelles can be formed through supramolecular self-assembly in solution,and the structural morphology is characterized by transmission electron microscopy as a nano spherical structure.defined as ball peptide.Compared with traditional linear peptides,the skin permeability of peptide within 2 h increased by 150%,and the anti enzymatic ability within 90 min increased by 156.8%.The efficacy verification experiments based on cell level showed that spherical nano peptides exhibited significant anti-aging effects.At the same time,it can be used as a delivery carrier to load other active molecules for transdermal absorption,and can be applied as a new type of peptide raw material in cosmetic products and formulations.
基金supported by a grant from the Ministry of Science and Technology,People's Republic of China(2023YFA0913500)a grant from the National Natural Science Foundation of China(32270347 and 32470348)to Fang Changa grant from the China Post-doctoral Science Foundation(2023M740705)to Ying Yu.
摘要CLAVATA3/EMBRYO SURROUNDING REGION(CLE)peptides are among the most well-studied families of plant peptide hormones,playing essential roles in regulating a wide range of biological processes,including plant growth,development,and stress adaptation.In this review,we explore the structural diversity of CLE peptides across species and provide a comprehensive summary of the biological functions and signaling mechanisms of CLE peptides.We first discuss their roles in plant development,including stem cell homeostasis,meristem activity,vascular patterning,and reproductive organ formation.We then explore how CLE peptides contribute to plant responses to environmental stresses such as nutrient deficiency,drought,and heat.Additionally,we summarize recent insights into the crosstalk between CLE signaling and classical phytohormonal pathways.Finally,we outline current challenges and propose future directions.By integrating knowledge from developmental and stress biology,this review aims to promote a deeper understanding of CLE signaling in dynamic plant environments,leveraging this knowledge to enhance crop resilience and productivity in changing climates.
基金provided by Chicken Farmers of Canada,Canadian Hatching Egg Producers,Investment Agriculture Foundation of British Columbia(INV106,INV247)Amphoraxe Life Sciences Inc.Partial support for trainees were provided by Mitacs(IT28945,IT43363)+2 种基金University of VictoriaUniversity of British ColumbiaAmphoraxe Life Sciences Inc。
摘要Background The overuse of antibiotics in both veterinary and human medicine has resulted in the emergence of antibiotic-resistant bacteria,prompting a search for effective alternatives.Antimicrobial peptides(AMPs)are short,often cationic,peptide-based molecules with antimicrobial and immunomodulatory activity,which makes them promising alternatives to conventional antibiotics in poultry production.Results From a prior machine-learning-guided screen of 875 candidate AMPs against a wide bacterial panel,62exhibited activity against avian pathogenic Escherichia coli(APEC)and low in vitro hemolytic and cytotoxic activity.We selected three lead AMPs from this list(named TeRu4,TeBi1,and PeNi4),and evaluated their in vitro and in vivo efficacy,safety,and immunomodulatory potential for use in poultry farming.In animal experiments,AMPs were administered via in ovo injection on d 18 of embryonic development.In APEC challenge trials,yolk sacs were inoculated with APEC post-hatch to assess early chick mortality,while in pen trials,birds were raised in a commercial production setting for 35 d.For challenged birds,TeBi1(10μg/egg)significantly reduced culture-positive rates for APEC in the air sac and pericardium,increased body weight by 50%and reduced cytokine transcript levels by 10%-30%on d 7post hatch.In HD11 chicken macrophage-like cultured cells,TeRu4(16μg/mL)suppressed lipopolysaccharide(LPS)-induced pro-inflammatory cytokine transcript levels.In pen trials,TeRu4(20μg/egg)increased the survival probability of female birds by 4.9%,while TeBi1(20μg/egg)increased the survival probability of all birds by 4.4%,by d 35.Gene expression analysis revealed AMP-and sex-specific cytokine responses.In pen trials,no significant differences were observed in mean weights,feed conversion ratio(FCR),and flock uniformity on d 35.By integrating high-throughput in ovo automation with large-scale commercial pen trials,this study provides a systematic translational bridge from in silico AI discovery to field-relevant poultry production interventions.Conclusions These findings demonstrate that TeBi1 and TeRu4 are promising antibiotic alternatives that improve survival,modulate immune responses,and maintain normal growth performance in broiler chickens in this experimental setting.
基金support from the Natural Science Foundation of Fujian Province,China(No.2024J08025)Fuzhou University(No.511264)Fuzhou University Testing Fund of Precious Apparatus(No.2024T014).
摘要Nitrile oxide is a highly reactive species used for organic synthesis and bioconjugation.Herein,we developed a novel approach for disulfide formation and capping of N-terminal cysteine in peptides mediated by bromo nitrile oxide.1,1-Dibromoformaldoxime acts as the precursor for bromo nitrile oxide.This transformation proceeds under mild conditions with rapid kinetics,efficiently converting a broad range of thiophenols,thiols,and cysteine-containing native peptides into disulfides,cyclic disulfides,or thiazolidin-2-one oximes.Notably,oxidant-sensitive residues such as methionine,tyrosine,and tryptophan are well tolerated without over-oxidation.The compatibility with aqueous media further highlights its potential for the late-stage modification of native peptides and the derivatization of biologically active molecules.