Journal of Peptide Science最新文献_第4页

Identification of Potent Cell Penetrating, Nontoxic Peptides for Inhibiting MDM2–p53 Interactions: Characterization of Anticancer Peptides via Molecular Dynamics Simulations 鉴定有效的细胞穿透，无毒肽抑制MDM2-p53相互作用：表征抗癌肽通过分子动力学模拟

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-21 DOI: 10.1002/psc.70033

Pradeep Pant, Aman Sehgal, Tushar Gupta, Pradeep Sharma

{"title":"Identification of Potent Cell Penetrating, Nontoxic Peptides for Inhibiting MDM2–p53 Interactions: Characterization of Anticancer Peptides via Molecular Dynamics Simulations","authors":"Pradeep Pant, Aman Sehgal, Tushar Gupta, Pradeep Sharma","doi":"10.1002/psc.70033","DOIUrl":"https://doi.org/10.1002/psc.70033","url":null,"abstract":"<div>\u0000 \u0000 Inhibiting MDM2–p53 interactions is a crucial therapeutic strategy in cancer treatment, as it can restore the tumor suppressor activity of p53 and inhibit tumor progression. Peptide inhibitors have shown promise in targeting this interaction; however, their optimization for in vivo use often encounters challenges, particularly in cellular uptake. The present study addresses this limitation by identifying cell-penetrating peptides (CPPs) that are predicted to be nontoxic to humans and capable of inhibiting the MDM2–p53 interaction. We utilized a comprehensive CPP database to extract unmodified peptides, focusing on those predicted to be nontoxic. Selected candidates were subjected to molecular docking followed by 500-ns all-atom explicit-solvent molecular dynamics (MD) simulations, performed in triplicates, to evaluate their binding stability and affinity with MDM2. Binding affinity calculations using MM-PBSA, AREA AFFINITY, and PRODIGY revealed that two peptides consistently exhibited stable binding to MDM2 and demonstrated higher affinity compared with the p53 reference fragment. These peptides not only maintained favorable interactions throughout the simulations but also showed strong potential to disrupt MDM2–p53 binding and reactivate p53 function. The findings highlight these peptides as promising nontoxic anticancer agents and provide a strong foundation for the development of peptide-based therapeutics targeting the MDM2–p53 interaction.\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of Diastereomerically Pure Cetrorelix Acetate by Using Fmoc Solid-Phase Peptide Synthesis (SPPS) Strategy: A Commercially Viable Approach Fmoc固相肽合成（SPPS）策略合成非对映体纯醋酸头孢瑞克：一种可行的商业方法

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-19 DOI: 10.1002/psc.70030

Kiran Aluri, Srinivas Basavoju, Jagadeesh B. Rangisetty, Manik R. Pullagurla, Bhaskar R. Pitta

{"title":"Synthesis of Diastereomerically Pure Cetrorelix Acetate by Using Fmoc Solid-Phase Peptide Synthesis (SPPS) Strategy: A Commercially Viable Approach","authors":"Kiran Aluri, Srinivas Basavoju, Jagadeesh B. Rangisetty, Manik R. Pullagurla, Bhaskar R. Pitta","doi":"10.1002/psc.70030","DOIUrl":"https://doi.org/10.1002/psc.70030","url":null,"abstract":"<div>\u0000 \u0000 In the synthesis of cetrorelix via solid-phase peptide synthesis (SPPS) employing the Fmoc strategy, the racemization of L-arginine and L-serine was effectively minimized to below 0.5%. This reduction was achieved using the coupling agent HATU, the additive HOBt or HOAt, and the base TMP. Racemization was observed during the coupling of Fmoc-L-arginine(Pbf) and Fmoc-O-tert-butyl-L-serine on Rink Amide AM resin. A gradient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the separation of all the structurally closely related cetrorelix isomers. Optimized RP-HPLC conditions identified D-arginine and D-serine isomeric impurities as the closest eluting peaks to the main cetrorelix peak. Controlling these impurities to the lowest possible levels is essential for developing an efficient preparative HPLC purification process for the commercial production of cetrorelix. This stringent control ensures that the final product meets the high standards required for commercial production and therapeutic use.\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of Bioactive Peptides Through Peptide Scanning 通过肽扫描发现生物活性肽

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-10 DOI: 10.1002/psc.70029

Debora Iaculli, Steven Ballet

{"title":"Discovery of Bioactive Peptides Through Peptide Scanning","authors":"Debora Iaculli, Steven Ballet","doi":"10.1002/psc.70029","DOIUrl":"https://doi.org/10.1002/psc.70029","url":null,"abstract":"<div>\u0000 \u0000 Therapeutic peptides targeted at various diseases are becoming increasingly relevant for the pharmaceutical industry. Several of these drugs were originally designed by mimicking a segment of a protein of interest. As such, protein mimicry represents a promising strategy both in immunology, for the identification of B- and T-cell epitopes, as well as for the modulation of protein activity, including the disruption of protein–protein interactions (PPIs) and the interference with biological or pathological cellular functions. Several methods have been developed to pinpoint the (binding) epitopes of a protein or the regions responsible for biological activity. One of such strategies is the scanning of the protein or selected domains with synthetic overlapping peptides. As the mechanism of action of a mimetic peptide can be similar to that of the whole protein, this method offers a powerful tool for the investigation of protein function, along with providing a solid basis for the development of therapeutic candidates. This review gives a general overview of different applications of the peptide scanning methodology, describing a comparison of the preparation and use of solid-phase libraries (peptide arrays) with isolated peptide libraries and highlighting their strengths and most common applications.\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytosolic Delivery of Functional Ubiquitin 功能性泛素的胞质递送

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-08 DOI: 10.1002/psc.70026

JoLynn B. Giancola, Aniekan Okon, Yanfeng Li, Eric R. Strieter, Ronald T. Raines

引用次数: 0

Synthesis of Stylissamide B, a Pro-Rich Cyclic Heptapeptide Isolated From the Marine Sponge Stylissa caribica 从加勒比海海绵体中分离的亲富环七肽花柱酰胺B的合成

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-07 DOI: 10.1002/psc.70028

Yitong Li, Hanyu Ling, Kenta Teruya, Hiroyuki Konno

引用次数: 0

In Vivo Evaluation of Pam2Cys-Modified Cancer-Testis Antigens as Potential Self-Adjuvanting Cancer Vaccines pam2cys修饰的癌睾丸抗原作为潜在的自佐剂癌症疫苗的体内评价

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-06 DOI: 10.1002/psc.70022

Salwa Aljohani, Alex G. Edmonds, Valeria Castelletto, Jani Seitsonen, Ian W. Hamley, Peter Symonds, Victoria A. Brentville, Lindy G. Durrant, Nicholas J. Mitchell

引用次数: 0

Antimicrobial and Potent Anti-Biofilm Properties of Rationally Designed α-Helix Antimicrobial Peptides 合理设计α-螺旋抗菌肽的抗菌和强效抗生物膜性能

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-06 DOI: 10.1002/psc.70027

Motasim Ismael, Khayeli Juliah, Madivoli Edwin

{"title":"Antimicrobial and Potent Anti-Biofilm Properties of Rationally Designed α-Helix Antimicrobial Peptides","authors":"Motasim Ismael, Khayeli Juliah, Madivoli Edwin","doi":"10.1002/psc.70027","DOIUrl":"https://doi.org/10.1002/psc.70027","url":null,"abstract":"<div>\u0000 \u0000 The antimicrobial resistance (AMR) crisis represents a significant global threat. Unlike traditional antibiotics, antimicrobial peptides offer a promising pathway because of their primary mechanisms. This study aimed to evaluate and rationally design novel AMPs based on tobacco nectar's AMP (Pep 6) to combat antibiotic resistance issues. Substitution and truncation of some amino acids were applied. Four peptides, KF19, KF16, LK16, and LR16, were designed with enhanced net charge hydrophobicity. They were evaluated for their in vitro antibacterial activity. However, only promising AMPs were further evaluated for their hemolytic activity, time-killing kinetics, mode of action, and anti-biofilm properties. The results showed that only KF19 and LR16 have potent activity against Staphylococcus aureus ATCC25923 and resistant isolates with MIC values from 7.81 to 15.62 μg/mL. Hemolysis ratios were 2.38% and 2.24% at 125 μg/mL for KF19 and LR16, respectively. Both peptides were able to kill S. aureus ATCC25923 within 2 h. SEM results showed their ability to target the cell membrane. Both peptides destroyed the S. aureus biofilms significantly at 62.5 and 125 μg/mL (**p < 0.01, ***p < 0.001, ****p < 0.0001). This study supported rational design in developing new antibacterial agents and demonstrated the therapeutic potency of novel peptides that could solve the resistance issues.\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N- to C-Peptide Synthesis, Arguably the Future for Sustainable Production N- to - c肽合成，可持续生产的未来

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-05-01 DOI: 10.1002/psc.70019

Kinshuk Ghosh, William D. Lubell

{"title":"N- to C-Peptide Synthesis, Arguably the Future for Sustainable Production","authors":"Kinshuk Ghosh, William D. Lubell","doi":"10.1002/psc.70019","DOIUrl":"https://doi.org/10.1002/psc.70019","url":null,"abstract":"A revolution in peptide production arrived from the innovation of carboxylate to amine C- to N-direction solid-phase synthesis. This cornerstone of modern peptide science has enabled multiple academic and industrial applications; however, the process of C- to N-solid phase peptide synthesis (C-N-SPPS) has extreme process mass intensity and poor atom economy. Notably, C-N-SPPS relies upon the use of atom-intensive protecting groups, such as the fluorenylmethyloxycarbonyl (Fmoc) protection and wasteful excess of protected amino acids and coupling agents. On the other hand, peptide synthesis in the amine to carboxylate N- to C-direction offers potential to minimize protection and may arguably enable more efficient means for manufacturing peptides. For example, efficient amide bond formation in the N- to C-direction has been accomplished using methods employing thioesters, vinyl esters, and transamidation to achieve peptide synthesis with minimal epimerization. This review aims to provide an overview of N- to C-peptide synthesis indicating advantages in taking this avenue for sustainable peptide production.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antimicrobial Activity of Short Analogues of the Marine Peptide EeCentrocin 1: Synthesis of Lipopeptides and Head-to-Tail Cyclic Peptides and Mechanism of Action Studies 海洋肽eecentrrocin 1短类似物的抗菌活性：脂肽和首尾环肽的合成及其作用机制研究

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-04-28 DOI: 10.1002/psc.70025

Danijela Simonovic, Hymonti Dey, Natascha Johansen, Trude Anderssen, Ida K. Ø. Hansen, Hege Devold, Terje Vasskog, Hans-Matti Blencke, Frode Jacobsen Øyen, Elizabeth G. Aarag Fredheim, Tor Haug, Morten B. Strøm

{"title":"Antimicrobial Activity of Short Analogues of the Marine Peptide EeCentrocin 1: Synthesis of Lipopeptides and Head-to-Tail Cyclic Peptides and Mechanism of Action Studies","authors":"Danijela Simonovic, Hymonti Dey, Natascha Johansen, Trude Anderssen, Ida K. Ø. Hansen, Hege Devold, Terje Vasskog, Hans-Matti Blencke, Frode Jacobsen Øyen, Elizabeth G. Aarag Fredheim, Tor Haug, Morten B. Strøm","doi":"10.1002/psc.70025","DOIUrl":"https://doi.org/10.1002/psc.70025","url":null,"abstract":"<div>\u0000 \u0000 We have synthesised a series of 12-residue analogues of a previously reported lead peptide (P6) developed from the heavy chain of the marine peptide EeCentrocin 1, isolated from the sea urchin Echinus esculentus. We optimised the lead peptide by increasing its net positive charge, its lipophilicity through N-terminal fatty acid acylation or incorporation of a Trp residue, and by synthesising head-to-tail cyclic peptides under pseudo–high-dilution conditions. All peptides were screened for antimicrobial and antifungal activity, and toxicity was determined against human red blood cells. The two most potent peptide analogues were the linear peptide P6-W6R8 and its head-to-tail cyclic analogue cP6-W6R8 displaying minimum inhibitory concentrations of 0.4–6.6 μM against Gram-positive and Gram-negative bacteria and 6.2–13 μM against fungi. All peptides showed low haemolytic activity except for two of the lipopeptides, in which haemolytic activity correlated with increasing acyl chain length. Mode of action studies using bacterial biosensor strains revealed a membrane disruptive effect of both the linear and the cyclic peptide. Overall, the results of our study demonstrated that relatively simple structural modifications could be successfully employed in the development of potent antimicrobial lead peptides derived from marine natural products.\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficient Screening of α-Glucosidase Inhibitory Peptides From Seahorse Through the Innovative Joint Technique: De Novo Sequencing and Parallel SPOT Synthesis 通过创新的联合技术：从头测序和平行点合成高效筛选海马α-葡萄糖苷酶抑制肽

IF 1.8 4区生物学

Journal of Peptide Science Pub Date : 2025-04-28 DOI: 10.1002/psc.70023

Shengfang Gao, Yimeng Li, Xiaohui Zhang, Zhuo Cao, Youyou Guo, Runkun Zhao, Lifan Li, Hongying Lin, Qi Qin, Bingqing Yi, Guodong Zhao

{"title":"Efficient Screening of α-Glucosidase Inhibitory Peptides From Seahorse Through the Innovative Joint Technique: De Novo Sequencing and Parallel SPOT Synthesis","authors":"Shengfang Gao, Yimeng Li, Xiaohui Zhang, Zhuo Cao, Youyou Guo, Runkun Zhao, Lifan Li, Hongying Lin, Qi Qin, Bingqing Yi, Guodong Zhao","doi":"10.1002/psc.70023","DOIUrl":"https://doi.org/10.1002/psc.70023","url":null,"abstract":"<div>\u0000 \u0000 In this research, de novo sequencing was innovatively combined with parallel SPOT synthesis for the efficient screening of biological peptides from TCM or seafood: seahorse with synergistic antioxidant and α-glucosidase inhibitory activities, which is promising for postprandial hyperglycemia management. Gastrointestinal digestion mimic and de novo sequencing were sequentially carried out to predict new peptides from seahorse. After bioinformatic analysis using Peptide Ranker, 82 peptides were eventually synthesized by efficient parallel SPOT technique, and Ser-Val-Try-Leu-Gly-Gly-Ser-Leu-Leu (SVWLGGSLL) was screened out as the most efficient peptide with synergistic antioxidant (DPPH radical scavenging activity of 77%) and α-glucosidase inhibitory activity (IC50 = 0.36 mM). Molecular docking was further carried out to illustrate the favorable ligand-receptor interactions formed such as hydrogen bonding and van der Waals force with low binding free energy of −7.8 kcal/mol. Moreover, pharmacokinetic analysis indicated that SVWLGGSLL was unrelated to toxicity with the advantage of gastrointestinal stability.\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0