Mrinal Kalita, Khushboo Yadav, Archana Archana, Thiruvancheril G. Gopakumar, Prema G. Vasudev, Ramesh Ramapanicker
{"title":"Incorporation of phenylcarbonyl groups in the sidechain: A tool to induce ordered assembly of peptides on surfaces","authors":"Mrinal Kalita, Khushboo Yadav, Archana Archana, Thiruvancheril G. Gopakumar, Prema G. Vasudev, Ramesh Ramapanicker","doi":"10.1002/psc.3629","DOIUrl":"10.1002/psc.3629","url":null,"abstract":"<p>The possibility of introducing various functionalities on peptides with relative ease allows them to be used for molecular applications. However, oligopeptides prepared entirely from proteinogenic amino acids seldom assemble as ordered structures on surfaces. Therefore, sidechain modifications of peptides that can increase the intermolecular interactions without altering the constitution of a given peptide become an attractive route to self-assembling them on surfaces. We find that replacing phenylalanine residues with unusual amino acids that have phenylcarbonyl sidechains in oligopeptides increases the formation of ordered self-assembly on a highly ordered pyrolytic graphite surface. Peptides containing the modified amino acids provided extended long-range ordered assemblies, while the analogous peptides containing phenylalanine residues failed to form long-range assemblies. X-ray crystallographic analysis of the bulk structures of these peptides and the analogous peptides containing phenylalanine residues reveal that such modifications do not alter the secondary structure in crystals. It also reveals that the secondary hydrogen bonding interaction through phenylcarbonyl sidechains facilitates extended growth of the peptides on graphite.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427106","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":"FDA's stamp of approval: Unveiling peptide breakthroughs in cardiovascular diseases, ACE, HIV, CNS, and beyond","authors":"Othman Al Musaimi","doi":"10.1002/psc.3627","DOIUrl":"10.1002/psc.3627","url":null,"abstract":"<p>Peptides exhibit significant specificity and effective interaction with therapeutic targets, positioning themselves as key players in the global pharmaceutical market. They offer potential treatments for a wide range of diseases, including those that pose significant challenges. Notably, the peptide trofinetide (Daybue) marked a groundbreaking achievement by providing the first-ever cure for Rett syndrome, and several peptides have secured FDA approval as first-in-class medications. Furthermore, peptides are expanding their presence in areas traditionally dominated by either small or large molecules. A noteworthy example is the FDA approval of motixafortide (Aphexda) as the first peptide-based chemokine antagonist. Here, the focus will be on the analysis of FDA-approved peptides, particularly those targeting cardiovascular diseases, human immunodeficiency, central nervous system diseases, and various other intriguing classes addressing conditions such as osteoporosis, thrombocytopenia, Cushing's disease, and hypoglycemia, among others. The review will explore the chemical structures of the peptides, their indications and modes of action, the developmental trajectory, and potential adverse effects.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419557","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}
Om Shanker Tiwari, Varun Rawat, Hang Zhang, Sonika Chibh, Sigal Rencus-Lazar, Charles E. Diesendruck, Ehud Gazit
{"title":"Ring-opening polymerization of lactide catalyzed using metal-coordinated enzyme-like amino acid assemblies","authors":"Om Shanker Tiwari, Varun Rawat, Hang Zhang, Sonika Chibh, Sigal Rencus-Lazar, Charles E. Diesendruck, Ehud Gazit","doi":"10.1002/psc.3626","DOIUrl":"10.1002/psc.3626","url":null,"abstract":"<p>Polylactide (PLA), a biocompatible and biodegradable polymer, is widely used in diverse biomedical applications. However, the industry standard for converting lactide into PLA involves toxic tin (Sn)-based catalysts. To mitigate the use of these harmful catalysts, other environmentally benign metal-containing agents for efficient lactide polymerization have been studied, but these alternatives are hindered by complex synthesis processes, reactivity issues, and selectivity limitations. To overcome these shortcomings, we explored the catalytic activity of Cu-(Phe)<sub>2</sub> and Zn-(Phe)<sub>2</sub> metal-amino acid co-assemblies as potential catalysts of the ring-opening polymerization (ROP) of lactide into PLA. Catalytic activity of the assemblies was monitored at different temperatures and solvents using <sup>1</sup>H-NMR spectroscopy to determine the catalytic parameters. Notably, Zn-(Phe)<sub>2</sub> achieved >99% conversion of lactide to PLA within 12 h in toluene under reflux conditions and was found to have first-order kinetics, whereas Cu-(Phe)<sub>2</sub> exhibited significantly lower catalytic activity. Following Zn-(Phe)<sub>2</sub>-mediated catalysis, the resulting PLA had an average molecular weight of 128 kDa and a dispersity index of 1.25 as determined by gel permeation chromatography. Taken together, our minimalistic approach expands the realm of metal-amino acid-based supramolecular catalytic nanomaterials useful in the ROP of lactide. This advancement shows promise for the future design of simplified biocatalysts in both industrial and biomedical applications.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3626","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176001","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}
{"title":"A comprehensive study on the identification and characterization of degradation products of lipoglycopeptide Dalbavancin using LC and LC-HRMS/MS","authors":"Sree Teja Paritala, Nitish Sharma, Ravi P. Shah","doi":"10.1002/psc.3608","DOIUrl":"10.1002/psc.3608","url":null,"abstract":"<p>Dalbavancin is the second-generation approved semisynthetic lipoglycopeptide by the United States Food and Drug Administration (USFDA) for the treatment of acute bacterial skin and skin-structure infections. Unlike other lipoglycopeptides, the stability behavior of Dalbavancin was least explored, which is a prerequisite. The current study endeavors to elucidate the oxidative and hydrolytic stability behavior of Dalbavancin by exposing the drug to oxidative, acidic, and basic stress conditions. A simple liquid chromatography (LC) method was developed, where significant resolution between Dalbavancin, its homologs, and the generated degradation products was achieved. Seven degradation products were identified under acidic, basic, and oxidative stress conditions. Using liquid chromatography and high-resolution mass spectrometry (LC-HRMS), MS/MS studies, the generated degradation products were identified and characterized. Formation of isomeric degradation products was identified especially upon exposure to basic stress conditions. The mechanistic fragmentation pathway for the seven degradation products was established, and the chemical structure for the identified degradation products was elucidated. The results strongly suggest that Dalbavancin is highly susceptible to degradation under oxidative and hydrolytic stress conditions. This study provides insights into the hydrolytic and oxidative stability of Dalbavancin, which can be employed during drug development and discovery in synthesizing relatively stable analogs.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945239","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":"Beyond the venom: Exploring the antimicrobial peptides from Androctonus species of scorpion","authors":"Vinutha Anandhan Sujatha, Chandrasekhar Gopalakrishnan, Amarnath Anbarasu, Chandra Sekar Ponnusamy, Rajkumar Choudhary, Sree Agash Saravanan Geetha, Rajasekaran Ramalingam","doi":"10.1002/psc.3613","DOIUrl":"10.1002/psc.3613","url":null,"abstract":"<p>Prevalent worldwide, the <i>Androctonus</i> scorpion genus contributes a vital role in scorpion envenoming. While diverse scorpionisms are observed because of several different species, their secretions to protect themselves have been identified as a potent source of antimicrobial peptide (AMP)-like compounds. Distinctly, the venom of these species contains around 24 different AMPs, with definite molecules studied for their therapeutic potential as antimicrobial, antifungal, antiproliferative and antiangiogenic agents. Our review focuses on the therapeutic potential of native and synthetic AMPs identified so far in the <i>Androctonus</i> scorpion genus, identifying research gaps in peptide therapeutics and guiding further investigations. Certain AMPs have demonstrated remarkable compatibility to be prescribed as anticancer drug to reduce cancer cell proliferation and serve as a potent antibiotic alternative. Besides, analyses were performed to explore the characteristics and affinities of peptides for membranes. Overall, the study of AMPs derived from the <i>Androctonus</i> scorpion genus provides valuable insights into their potential applications in medicine and drug development.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945241","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}
Linda Leone, Maria De Fenza, Alessandra Esposito, Ornella Maglio, Flavia Nastri, Angela Lombardi
{"title":"Peptides and metal ions: A successful marriage for developing artificial metalloproteins","authors":"Linda Leone, Maria De Fenza, Alessandra Esposito, Ornella Maglio, Flavia Nastri, Angela Lombardi","doi":"10.1002/psc.3606","DOIUrl":"10.1002/psc.3606","url":null,"abstract":"<p>The mutual relationship between peptides and metal ions enables metalloproteins to have crucial roles in biological systems, including structural, sensing, electron transport, and catalytic functions. The effort to reproduce or/and enhance these roles, or even to create unprecedented functions, is the focus of protein design, the first step toward the comprehension of the complex machinery of nature. Nowadays, protein design allows the building of sophisticated scaffolds, with novel functions and exceptional stability. Recent progress in metalloprotein design has led to the building of peptides/proteins capable of orchestrating the desired functions of different metal cofactors. The structural diversity of peptides allows proper selection of first- and second-shell ligands, as well as long-range electrostatic and hydrophobic interactions, which represent precious tools for tuning metal properties. The scope of this review is to discuss the construction of metal sites in de novo designed and miniaturized scaffolds. Selected examples of mono-, di-, and multi-nuclear binding sites, from the last 20 years will be described in an effort to highlight key artificial models of catalytic or electron-transfer metalloproteins. The authors' goal is to make readers feel like guests at the marriage between peptides and metal ions while offering sources of inspiration for future architects of innovative, artificial metalloproteins.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890696","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}
Andrea Öhlander, Carsten Lüdtke, Artur Sahakjan, Richard E. Johnsson
{"title":"N-Butylpyrrolidinone is an equally good solvent as N,N-dimethylformamide for microwave assisted solid phase peptide synthesis","authors":"Andrea Öhlander, Carsten Lüdtke, Artur Sahakjan, Richard E. Johnsson","doi":"10.1002/psc.3612","DOIUrl":"10.1002/psc.3612","url":null,"abstract":"<p>Solid-phase peptide synthesis (SPPS) is the prevailing method for synthesizing research peptides today. However, SPPS is associated with a significant environmental concern due to the utilization of hazardous solvents such as <i>N</i>,<i>N</i>-dimethylformamide (DMF) or <i>N</i>-methylpyrrolidone, which generate substantial waste. In light of this, our research endeavors to identify more environmentally friendly solvents for SPPS. In this study, we have assessed the suitability of five green solvents as alternatives to DMF in microwave assisted SPPS. The solvents evaluated include Cyrene, ethyl acetate, 1,3-dioxolane, tetrahydro-2-methylfuran, and <i>N</i>-Butylpyrrolidinone (NBP). Our investigation encompassed all stages of the synthesis process, from resin swelling, dissolution of reagents, culminating in the successful synthesis of five diverse peptides, including the challenging ACP 65–74, Peptide 18A, Thymosin α1, and Jung-Redemann peptide. Our findings indicate that NBP emerged as a strong contender, performing on par with DMF in all tested syntheses. Furthermore, we observed that combinations of NBP with either ethyl acetate or tetrahydro-2-methylfuran demonstrated excellent results. This research contributes to the pursuit of more sustainable and environmentally conscious practices in peptide synthesis.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890657","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}
Mareike Schenk, Karin Mörl, Stephan Herzig, Annette G. Beck-Sickinger
{"title":"Targeted modulation of gene expression through receptor-specific delivery of small interfering RNA peptide conjugates","authors":"Mareike Schenk, Karin Mörl, Stephan Herzig, Annette G. Beck-Sickinger","doi":"10.1002/psc.3611","DOIUrl":"10.1002/psc.3611","url":null,"abstract":"<p>Small interfering RNA (siRNA) has emerged as a valuable tool to address RNA interference (RNAi) to modulate gene expression also in therapy. However, challenges such as inefficient cell targeting and rapid degradation in biological systems have limited its success. To address these issues, the development of a receptor-specific shuttle system represents a promising solution. [F<sup>7</sup>,P<sup>34</sup>]-NPY analogues were modified by solid-phase peptide synthesis, enabling non-covalent conjugation with siRNA. This modification yielded an efficient siRNA vehicle capable of binding and transporting its cargo into target cells without adversely affecting receptor activation or cell viability. Mass spectrometry and gel shift assays confirmed successful and stable siRNA binding under various conditions. Microscopy experiments further demonstrated the co-internalization of labeled peptides and siRNA in Hepa1c1 cells, highlighting the stability of the complex. In vitro quantitative RT-PCR experiments, targeting the TSC22D4 gene to normalize systemic glucose homeostasis and insulin resistance, revealed a functional peptide-based siRNA shuttle system with the ability to decrease mRNA expression to approximately 40%. These findings strengthen the potential of receptor-specific siRNA shuttle systems as efficient tools for gene therapy that offer a possibility for reducing side effects.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/psc.3611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876749","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}
Luigi Aloj, Rosalba Mansi, Stefania De Luca, Antonella Accardo, Diego Tesauro, Giancarlo Morelli
{"title":"Radiolabeled peptides and their expanding role in clinical imaging and targeted cancer therapy","authors":"Luigi Aloj, Rosalba Mansi, Stefania De Luca, Antonella Accardo, Diego Tesauro, Giancarlo Morelli","doi":"10.1002/psc.3607","DOIUrl":"10.1002/psc.3607","url":null,"abstract":"<p>There is an expanding body of evidence showing that synthetic peptides in combination with radioactive isotopes can be utilized for medical purposes. This area is of particular interest in oncology where applications in diagnosis and therapy are at different stages of development. We review the contributions in this area by the group originally founded by Carlo Pedone in Naples many years ago. We highlight the work of this group in the context of other developments in this area, focusing on three biologically relevant receptor systems: somatostatin, gastrin-releasing peptide, and cholecystokinin-2/gastrin receptors. We focus on key milestones, state of the art, and challenges in this area of research as well as the current and future outlook for expanding clinical applications.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865633","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":"A stability-indicating method development and validation for the determination of related substances in novel synthetic decapeptide by HPLC","authors":"Ramesh Pawar, Sunil Tivari, Divya Panchani, Jayanti Makasana","doi":"10.1002/psc.3610","DOIUrl":"10.1002/psc.3610","url":null,"abstract":"<p>In the present scenario, peptide is an emerging field of research having vast therapeutic applications. Diverse impurities may rise from various stages of the synthesis process and storage of the peptides. Because these contaminants may have an impact on the therapeutic safety and effectiveness of peptides in their approaching applications, they must be identified and carefully monitored. Considering the pharmaceutical importance of the extent of peptides, we were motivated to synthesize a decapeptide and establish a novel gradient reversed-phase high-performance liquid chromatography (RP-HPLC) method for its analysis along with efficient separation of its six related impurities. Different buffers, organic modifiers, and columns were used in the tests for good separation of these impurities. To establish a stability-indicating method, a stress study was also conducted. The International Conference on Harmonization (ICH) guidelines have been followed for validation of the developed analytical method. The validated method revealed sufficient accuracy, specificity, linearity, robustness, precision, and high sensitivity for its intended use. The proposed method could be appropriate for routine analysis and stability assessment of the decapeptide, which might be useful for further scientific investigation.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835240","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}