Peptide Science最新文献

{"title":"Empowering Antimicrobial Peptides: Harnessing Nanotechnology and Engineering Strategies to Combat Microbial Resistance","authors":"Dubey Avinash, Anjali Bisht, Manish Kumar, Shubham Thakur, Preeti Patel, Balak Das Kurmi","doi":"10.1002/pep2.24376","DOIUrl":"https://doi.org/10.1002/pep2.24376","url":null,"abstract":"Antimicrobial peptides (AMPs) are being studied for their potential in addressing microbial resistance, a significant issue in treating infections. More than 22,500 AMPs are listed in the database, but their clinical use faces challenges like instability and selectivity. Nanodrug delivery systems are now seen as a beneficial method to improve the effectiveness of AMPs. These systems can shield AMPs from degradation, enhance their availability, and deliver them to specific infection sites, enhancing their ability to combat resistance. One example is liposomal nanoparticles loaded with a mix of AMPs, targeting drug‐resistant bacteria directly. Strategies to develop novel AMPs through engineering methods, including design approaches, computational techniques, and modifications for stability, are discussed in this review. Combinatorial approaches with antibiotics, patents, and clinical trials involving AMPs against infections are also considered, highlighting the potential of AMPs in battling microbial resistance.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"15 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141885875","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}

{"title":"Food Protein‐Derived Zinc‐Binding Peptides: Isolation, Purification, and Biological Aspects","authors":"Nurkhodja Mukhamedov, Akmal M. Asrorov, Muzaffar Kayumov, Ahmidin Wali, Haji Akber Aisa, Sharafitdin Mirzaakhmedov, Abulimiti Yili","doi":"10.1002/pep2.24369","DOIUrl":"https://doi.org/10.1002/pep2.24369","url":null,"abstract":"Zinc is the second most valuable microelement after iron, according to its abundance in the human body. Supplementation of this metal is not straightforward because of several factors like phytates and interference of other minerals during gastrointestinal digestion. For the last several years, intensive research has been developing new forms of zinc supplements based on zinc‐binding peptides from food products. Except for the advantages of supplementation, zinc‐peptide complexes are expected to be drug candidates against various diseases. Zinc supplementation can be improved by protein hydrolysates and peptides due to their zinc‐binding ability. They enhance zinc supplementation and contribute to preventing conditions leading to zinc deficiency that cause various diseases. Research on food‐derived zinc‐binding peptides is progressing in two directions: the isolation and identification of individual peptides (1) and the preparation of zinc complexes of protein hydrolysates (2). Both approaches are primarily aimed at developing effective mineral supplements, although some work on the second approach is also related to nutrition and therapy. Because zinc–protein hydrolysate complexes are nonstandardized mixtures of peptides, their biological activity mechanisms can be difficult to study. Therefore, it is important to focus more research on the biological activity of individual zinc‐binding complexes and their zinc complexes. This work reviewed recent advances in isolating and identifying zinc‐binding peptides from food sources, preparing protein hydrolysate–zinc complexes, and their biological activities. The established sequences of zinc‐binding peptides have been compiled into a table to review their amino‐acid composition and sequence. We also highlighted approaches for isolating and determining the zinc‐binding capacity of peptides in this class. The structural features of peptides affecting their zinc‐binding property were discussed in one section.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"67 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777242","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}

{"title":"Disruption of the LRRK2‐FADD Interface Using Constrained Peptides","authors":"Krista K. Alexander, Michalis Kentros, Leah G. Helton, Dimitris Tantis‐Tapeinos, Timothy J. LeClair, Fredejah T. Royer, Neil J. Grimsey, Alexia V. Polissidis, Eileen J. Kennedy, Hardy J. Rideout","doi":"10.1002/pep2.24374","DOIUrl":"https://doi.org/10.1002/pep2.24374","url":null,"abstract":"Mutations in the gene encoding leucine‐rich repeat kinase 2 (<jats:italic>LRRK2</jats:italic>) are the most common cause of familial Parkinson's disease (PD). The reduced penetrance of mutations in the LRRK2 gene has also led to variants appearing in seemingly sporadic forms of the disease. Kinase inhibition effectively blocks neuronal death and small‐molecule Class I inhibitors are proceeding through clinical trials in multiple PD cohorts. The toxic interaction between mutant LRRK2 and FADD lies downstream of its kinase activity and is required to induce neuronal death. The present study aimed to determine whether the FADD‐LRRK2 interface could be disrupted and what effects this may have on neuroprotection. A series of constrained peptides were designed to mimic the alpha‐helical protein interaction interface between the LRRK2 armadillo region and the death domain of FADD. These peptide‐based protein–protein interaction inhibitors significantly reduced this interaction and blocked apoptotic death of primary neurons expressing G2019S‐LRRK2. This work has identified novel constrained peptides that disrupt the LRRK2‐FADD interface and downregulate mutant LRRK2‐induced neuronal death in an allosteric manner, thereby providing a potential alternative therapeutic approach for PD.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"24 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777243","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}

{"title":"The Role of Structural Flexibility in Hydrocarbon‐Stapled Peptides Designed to Block Viral Infection via Human ACE2 Mimicry","authors":"Sicheng Jiang, Yu Tian, Vlad Nicolaescu, Aslan Mansurov, Glenn Randall, Matthew V. Tirrell, James L. LaBelle","doi":"10.1002/pep2.24375","DOIUrl":"https://doi.org/10.1002/pep2.24375","url":null,"abstract":"The COVID‐19 pandemic drove a uniquely fervent pursuit to explore the potential of peptide, antibody, protein, and small‐molecule‐based antiviral agents against severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). The interaction between the SARS‐CoV2 spike protein with the angiotensin‐converting enzyme 2 (ACE2) receptor that mediates viral cell entry was a particularly interesting target given its well‐described protein–protein interaction (PPI). This PPI is mediated by an α‐helical portion of ACE2 binding to the receptor binding domain (RBD) of the spike protein and thought to be susceptible to blockade through molecular mimicry. Small numbers of hydrocarbon‐stapled synthetic peptides designed to disrupt or block this interaction were tested individually and were found to have variable efficacy despite having related or overlapping sequences and similarly increased α‐helicity. Reasons for these differences are unclear and reported preclinical successes have been limited. This study sought to better understand reasons for these differences through evaluation of a comprehensive collection of hydrocarbon‐stapled peptides, designed based on four distinct principles: stapling position, number of staples, amino acid sequence, and primary sequence length. Surprisingly, we observed that the helicity and amino acid sequence iterations of hydrocarbon‐stapled peptides did not correlate with their bioactivity. Our results highlight the importance of iterative and combinatorial testing of these compounds to determine a configuration that best mimics natural binding and allows for chain flexibility while sacrificing structural helicity.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"3 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141740307","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}

{"title":"In Silico Structural and Functional Characterization of the Thaumatin‐Like Gene Family in Phaseolus lunatus Reveals the Potential for Microbial and Antiviral Activity","authors":"Dalton Ferreira Matos, Maria Cidinaria Silva Alves, Ruana Carolina Cabral da Silva, Hortência E. P. Santana, Denise Santos Ruzene, Marcus Vinicius de Aragão Batista, Daniel P. Silva","doi":"10.1002/pep2.24373","DOIUrl":"https://doi.org/10.1002/pep2.24373","url":null,"abstract":"Thaumatin‐like proteins (TLPs) are part of the pathogenesis‐related (PR) proteins that are important in host plant defense. TLPs have multiple defense functions against pathogens (bacteria, viruses, and fungi) and are involved in other biological processes of several living organisms. However, the biological role of TLPs must be elucidated for other species, such as <jats:italic>Phaseolus lunatus</jats:italic>, popularly known as lima bean. In this study, we propose to investigate the biological activity of TLPs in <jats:italic>P. lunatus</jats:italic>, which can help develop a detailed functional characterization of the <jats:italic>TLP</jats:italic> gene in other crop cultures. As a result, a total of 31 <jats:italic>PlTPLs</jats:italic> genes and 16 highly conserved cysteine residues for each family member were identified in the lima bean genome. Regarding phylogenetic analysis, 128 TLPs from different plant species, including <jats:italic>P. lunatus</jats:italic>, were used, and the phenetic tree revealed that the TLPs could be divided into six groups. The leading group was Group 4, containing 34 TLPs; the smallest was Group 7, containing only a single TLP. The analysis of antimicrobial and antiviral activity revealed that 27 PlTLPs have antimicrobial activity and 7 PlTLPs have potential antiviral activity. For chromosomal distribution of the <jats:italic>PlTLPs</jats:italic>, 8 of 11 chromosomes presented at least one <jats:italic>PlTLs</jats:italic> on one of the chromosomes. Finally, molecular modeling was carried out between two TLPs (PlTLP5 and PlTLP14), which presented antimicrobial and antiviral activity and did not have allergenic activity. The results showed that the two candidates presented ≥90% of their residues in the favorable regions and ∼10% in the permitted regions, demonstrating that the two PlTLPs are considered promising targets for biotechnological applications, especially those related to the genetic improvement of agricultural crops and the development of antimicrobial agents.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"25 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141739793","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}

{"title":"Integrated Pharmacognostic and Computational Analysis of Hydrocotyle javanica Thunb. Phytochemicals as a Potential HER2 Tyrosine Kinase Inhibitor in Breast Cancer","authors":"Anjini Bellai, Satyendra Deka, Hui Tag, Kunal Bhattacharya, Pallabi Kalita Hui","doi":"10.1002/pep2.24372","DOIUrl":"https://doi.org/10.1002/pep2.24372","url":null,"abstract":"Breast cancer ranks as a leading cause of mortality, primarily affecting females. With the reported side effects of conventional anticancer drugs, herbal sources have emerged as an effective alternative for the treatment of various severe diseases like cancer. <jats:italic>Hydrocotyle javanica</jats:italic> Thunb. (<jats:italic>H. javanica</jats:italic>) is a perennial herb belonging to Araliaceae family. This study explored the ethnobotanical use of <jats:italic>H. javanica</jats:italic>, its pharmacognosy, antioxidant, and phytochemical characterization using liquid chromatography‐mass spectrometry tool, and molecular docking against breast cancer receptor, human epidermal growth factor receptor‐2 (HER2). The study revealed morphological, microscopic diagnostic features, and physicochemical properties of <jats:italic>H. javanica</jats:italic>. Methanolic extract of <jats:italic>H. javanica</jats:italic> (MEHJ) displayed dose‐dependent antioxidant activities. LC–MS analysis characterized metabolites of flavonoids, phenolic acids, triterpenoid, and triterpenoid saponin. Phytochemicals including chlorogenic acid, astragalin, and hyperoside, displayed the most favorable binding affinity with HER2 during molecular docking. These phytochemicals also possessed significant drug‐likeness characteristics. Furthermore, molecular dynamic simulation demonstrated stable interaction between these phytochemicals and HER2, suggesting a potential inhibitor of HER2, a crucial target in breast cancer treatment. Therefore, the present study offers an opportunity for further research and development of anticancer drugs derived from <jats:italic>H. javanica.</jats:italic>","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"22 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609932","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}

{"title":"Molecular Mechanisms of Buzhong Yiqi Decoction in the Treatment of Gastric Cancer: A Network Pharmacology, Molecular Docking, and In Vitro Experimental Analysis","authors":"Panke Zeng, Xinyu Wu, Chen Chen, Jianing Zhang, Haroon ur Rashid, Pengfei Zhang","doi":"10.1002/pep2.24371","DOIUrl":"https://doi.org/10.1002/pep2.24371","url":null,"abstract":"Gastric cancer (GC) is the most common type of cancer of the digestive system with high morbidity and mortality. Chemotherapy and targeted therapy are used to treat patients with advanced GC. However, side effects and drug resistance to the two modalities remain the main challenges. The Buzhong Yiqi decoction (BZYQD), a classical traditional Chinese medicine formula, has been reported for the treatment of various types of cancers. However, the underlying pharmacological mechanism has not been fully elucidated. Therefore, this study integrated network pharmacology, molecular docking, cancer public databases, and cell experiments to explore the potential bioactive compounds and BZYQD's mechanism of action against GC. A total of 245 targets of BZYQD, 5291 GC‐related targets, and 186 were identified as their common targets through the database. Network analysis confirmed AKT1, TP53, TNF, and EGFR to be the core targets, while the main compounds observed were quercetin, kaempferol, and β‐Sitosterol. The core signaling pathways included PI3K‐AKT, MAPK, TNF, and IL‐17. Molecular docking revealed good binding activity for the main compounds and core targets. Based on the database's validation of core targets, a large number of core genes were verified to be consistent with this study. Quercetin, kaempferol, and β‐Sitosterol were found to significantly reduce the growth of GC cells in the MTT experiment. The current study revealed that BZYQD may inhibit GC progression by interfering with core targets such as AKT1, TP53, TNF, EGFR, and MAPK3, and by regulating the activity of PI3K‐AKT, MAPK, TNF, and IL‐17 signaling pathways.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"14 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141548870","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}

{"title":"Chemically Peptide Synthesis and Role of Arginine and Lysine in the Antimicrobial and Antiviral Activity of Synthetic Peptides: A Comprehensive Review","authors":"Selin Zeynep Sunar, Tayfun Acar, Fikrettin Sahin","doi":"10.1002/pep2.24368","DOIUrl":"https://doi.org/10.1002/pep2.24368","url":null,"abstract":"This review examines the potential applications of peptides in biotechnology, medicine, and pharmacy, while highlighting the important antibacterial and antiviral properties of peptides. Peptides and chemical peptide synthesis have become a field of study that is gaining great momentum today. Some of the main reasons for this are high specificity, biodegradability and versatility of peptides. Peptides also have some specific properties that make them attractive for pharmaceutical development. As a case study, it can be used to create peptides that can be used to replace or fix damaged proteins in the body by mimicking the action of naturally occurring proteins. Delivering drugs or other therapeutic agents to specific cells or tissues is another method that can help increase the effectiveness of treatment and reduce unwanted effects. Various types of antimicrobial peptides (AMPs), such as defensins and cathelicidins, and their anti‐infective properties are also discussed. Finally, peptides (melittin, lactoferricin, etc.) can be used to trigger an immune response against certain infections, such as COVID‐19 and Zika virus, by acting as vaccines. In our study, a comprehensive review was made on antiviral and AMPs, and especially peptides containing arginine and lysine were mentioned. The properties of these peptides, examples of these peptides and their developments in the pharmaceutical field are emphasized.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"50 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141530205","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}

{"title":"Structure–Function Relationship and Stability of Latroeggtoxin‐VI: A Proteinaceous Toxin From the Eggs of Latrodectus tredecimguttatus","authors":"Si Chen, Minglu Sun, Panfeng Yin, Xianchun Wang","doi":"10.1002/pep2.24367","DOIUrl":"https://doi.org/10.1002/pep2.24367","url":null,"abstract":"Latroeggtoxin‐VI (LETX‐VI), a peptide toxin discovered from the eggs of spider <jats:italic>Latrodectus tredecimguttatus</jats:italic>, was previously shown to promote the synthesis and release of dopamine in rat pheochromocytoma (PC12) cells, showing potential applications in the neurobiology and medicine. To further understand the structure and properties of LETX‐VI, the key residues were identified and their roles in the structure, function, and stability of LETX‐VI were analyzed in the present work. Based on the protein molecular docking, our previous work, and the relevant literature, the potential key residues of LETX‐VI were selected and identified by alanine‐scanning mutagenesis. The wild‐type LETX‐VI and its 13 mutants, including a double mutant, were prepared by gene cloning and heterologous expression in <jats:italic>Escherichia coli</jats:italic>, followed by activity, structure, and stability determination. The results demonstrated that the activity of the mutants K25A, R35A, K40A/R41A, and L45A, particularly R35A, to promote dopamine release from PC12 cells was significantly decreased compared with that of the wild‐type LETX‐VI, indicating that these mutated residues are the key residues. Circular dichroism (CD) analysis showed that the secondary structure of these mutants was not obviously different from that of wild‐type LETX‐VI, suggesting that mutation‐caused decrease in the activity of LETX‐VI is due to the changes in the binding site on the molecule surface, rather than the abnormal alternation of the molecular conformation of LETX‐VI. Acetonitrile (ACN) did not obviously influence the activity of LETX‐VI; however, 0.1% trifluoroacetic acid (TFA) treatment for 2 h significantly reduced its activity. Treatment with weakly acidic and basic buffers (pH ≥ 6.6) for 12 h was favorable for LETX‐VI and R35A to exert their activity. Higher temperatures (&gt;37°C) decreased the activity of both wild‐type LETX‐VI and R35A. In conclusion, K25, R35, K40, R41, and L45 particularly R35 are the important functional site residues; during experiments, care should be taken to avoid the adverse influence of strong acid and high temperature on LETX‐VI. These observations have enhanced our understanding of the structure and properties of LETX‐VI and provided references for the subsequent modification of structure and function of LETX‐VI.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"28 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510809","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}

{"title":"From Protein to a Bioactive Peptide: Potent IL‐6 Peptide Antagonist Generated by a Novel Method","authors":"Alexander Pisarchik, Noreen Gervasi, Edmund Nesti","doi":"10.1002/pep2.24370","DOIUrl":"https://doi.org/10.1002/pep2.24370","url":null,"abstract":"Here, we describe a new technology, designed to accelerate peptide discovery by quick identification and optimization of the residues critical for protein–protein interactions or ligand binding. We called it PepFusion. It is based on ligation of short DNA sequences generated from known ligand‐binding regions. We tested it by selecting peptide antagonists of interleukin‐6 (IL‐6), a key mediator of inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease, and Castleman disease (CD). The PepFusion library demonstrated superiority over a random library by yielding a peptide with low micromolar affinity for IL‐6, whereas the random library failed. The affinity of the peptide from the PepFusion library was further enhanced by additional rounds of mutagenesis leading to peptide variants with low nanomolar IL‐6 affinity. In addition to generating high‐affinity peptides, our method opens the way to solve the problem of the false positive sequences, which are common with all display technologies.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"50 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141510890","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}