{"title":"PepFuNN: Novo Nordisk Open-Source Toolkit to Enable Peptide in Silico Analysis","authors":"Rodrigo Ochoa, Kristine Deibler","doi":"10.1002/psc.3666","DOIUrl":"10.1002/psc.3666","url":null,"abstract":"<p>We present PepFuNN, a new open-source version of the PepFun package with functions to study the chemical space of peptide libraries and perform structure–activity relationship analyses. PepFuNN is a Python package comprising five modules to study peptides with natural amino acids and, in some cases, sequences with non-natural amino acids based on the availability of a public monomer dictionary. The modules allow calculating physicochemical properties, performing similarity analysis using different peptide representations, clustering peptides using molecular fingerprints or calculated descriptors, designing peptide libraries based on specific requirements, and a module dedicated to extracting matched pairs from experimental campaigns to guide the selection of the most relevant mutations in design new rounds. The code and tutorials are available at https://github.com/novonordisk-research/pepfunn.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950575","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}
Mrinal Kalita, Archana, Ramesh Ramapanicker, Prema G. Vasudev
{"title":"Crystallographic Analysis of Short Helical Peptides Containing Homologs of Phenylalanine","authors":"Mrinal Kalita, Archana, Ramesh Ramapanicker, Prema G. Vasudev","doi":"10.1002/psc.3667","DOIUrl":"10.1002/psc.3667","url":null,"abstract":"<div>\u0000 \u0000 <p>Interactions between aromatic side chains of amino acids stabilize the fold and assembly of short peptides. The aromatic π…π and C-H…π interactions have been widely explored in the design of short peptides with specific folding and aggregation patterns. In the present study, we investigated the effect of homologated phenylalanine side chains on the conformation and assembly of peptide helices through X-ray crystallographic structure determination and analysis of five pentapeptides. The parent peptide Boc-Phe-Aib-Aib-Leu-Phe-NHiPr (<b>1</b>) and its four variations were synthesized, in which either one or both of the Phe side chains have been modified by inserting one (homophenylalanine, hPhe; -CH<sub>2</sub>-CH<sub>2</sub>-C<sub>6</sub>H<sub>5</sub>) or two (h<sup>2</sup>Phe; -CH<sub>2</sub>-CH<sub>2</sub>-CH<sub>2</sub>-C<sub>6</sub>H<sub>5</sub>) additional CH<sub>2</sub> groups in the side chain, and their crystal structures were analyzed. The results show that intramolecular aromatic interactions are not present in the parent peptide but are present in the peptides containing the higher homologs of Phe. In peptides that did not show intramolecular aromatic interactions, the effect of increased length of the side chain of Phe residues manifested as intermolecular interactions leading to ordered packing in crystals. The results indicate the potential of hPhe and h<sup>2</sup>Phe residues to have aromatic interactions that could induce preferential folding and aggregation of peptides containing them.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907208","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}
Tuan Hiep Tran, Thanh Huong Le, Thi Thu Phuong Tran
{"title":"The Potential Effect of Endogenous Antimicrobial Peptides in Cancer Immunotherapy and Prevention","authors":"Tuan Hiep Tran, Thanh Huong Le, Thi Thu Phuong Tran","doi":"10.1002/psc.3664","DOIUrl":"10.1002/psc.3664","url":null,"abstract":"<div>\u0000 \u0000 <p>Antimicrobial peptides (AMPs) are crucial constituents of inherent immunity and serve as vital components of human host defense, playing a pivotal role in combating invading microbial pathogens. Beyond their antimicrobial functions, AMPs also exhibit various other biological activities including apoptosis induction, wound healing promotion, and immune modulation. These peptides are found in various exposed tissues or surfaces throughout the body, such as eyes, skin, mouth, ears, respiratory tract, lungs, digestive, and urinary system. Additionally, certain AMPs such as LL-37, HNP, and lactoferrin have shown potential as candidates for anticancer activity. Given the limited selectivity between normal and cancer cells exhibited by many current immunotherapeutic agents, the inherent properties of AMPs make them promising candidates for cancer treatment. Their abundance, bioavailability, safety profile, efficiency, and harmony with the host immune system position them as attractive tools in the fight against cancer. This review is aimed at exploring the potential anticancer properties of AMPs and elucidating their relationship with immunology and cancer immunotherapy.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882326","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":"Norleucine Substitution Enhances Self-Assembly of a Lanthanide-Binding Polypeptide Coiled Coil","authors":"Diego B. Sarte, Aaron Joseph L. Villaraza","doi":"10.1002/psc.3665","DOIUrl":"https://doi.org/10.1002/psc.3665","url":null,"abstract":"<div>\u0000 \u0000 <p>A de novo lanthanide-binding coiled-coil polypeptide (MB1–2) was previously reported to self-assemble into a trimeric complex upon addition of Tb<sup>3+</sup> with a micromolar range dissociation constant. This study examines the effect of substitution of hydrophobic residues in heptad repeats of MB1–2 on the thermodynamic stability of the resulting Tb-peptide complex. Substitution of isoleucine to norleucine in each heptad repeat was assessed considering the greater accessible surface area of the latter and predicted increased hydrophobic interaction. Job's method of continuous variation using circular dichroism spectroscopy suggests a trimeric structure for the analog complex equivalent to that formed by MB1–2. The dissociation constant and CD spectra suggest that complex formation in the analog is more favorable as a result of ligand preorganization. In addition, thermal denaturation suggests greater stability of the Tb-MB1–2 Nle complex in comparison to the parent Tb-MB1–2. These results indicate improved stability of the complex class can be achieved through heptad repeat amino acid substitutions that increase peptide interchain interaction.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861902","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}
Eri Ochiai, Yuki Takahashi, Shota Inokuchi, Akie Sumiya, Makoto Hasegawa
{"title":"cDNA Display Selection of Interacting Peptide Ligands of the Guanylate Cyclase C Receptor","authors":"Eri Ochiai, Yuki Takahashi, Shota Inokuchi, Akie Sumiya, Makoto Hasegawa","doi":"10.1002/psc.3663","DOIUrl":"10.1002/psc.3663","url":null,"abstract":"<div>\u0000 \u0000 <p>Guanylate cyclase C (GC-C), a receptor expressed on the apical membrane of intestinal mucosal cells, is activated by heat-stable enterotoxin (STa) produced by enterotoxigenic <i>Escherichia coli</i>, as well as the endogenous ligands guanylin and uroguanylin. In this study, novel peptides that interact with GC-C were generated using the cDNA display method, and their binding affinity and biological activity were evaluated. While the linear peptide library did not yield peptides with sufficient affinity for GC-C, three cyclic peptides (GCC-P1, GCC-P2, and GCC-P3), each containing two cysteine residues within a 15-residue sequence, were obtained from a cyclic peptide library containing nine-residue random sequences. GC-P2 exhibited significant binding affinity in Biacore assays, although the affinity was lower than those reported for known ligands. Notably, GCC-P2 and GCC-P3 demonstrated enhanced cGMP activity when used in combination with linaclotide. However, the agonist activity of these peptides was minimal, indicating that further modifications may be necessary to develop them for clinical applications. This study successfully extracted consensus sequences of peptide motifs that bind to GC-C from a highly diverse nine-residue random sequence library, which provides fundamental insights for the discovery and optimization of novel GC-C ligands.</p>\u0000 </div>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807438","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 memory of Prof. Luis Moroder","authors":"Yuji Kobayashi","doi":"10.1002/psc.3660","DOIUrl":"10.1002/psc.3660","url":null,"abstract":"","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729720","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 versatility of peptide hydrogels: From self-assembly to drug delivery applications","authors":"Julie Heremans, Steven Ballet, Charlotte Martin","doi":"10.1002/psc.3662","DOIUrl":"10.1002/psc.3662","url":null,"abstract":"<p>Pharmaceuticals often suffer from limitations such as low solubility, low stability, and short half-life. To address these challenges and reduce the need for frequent drug administrations, a more efficient delivery is required. In this context, the development of controlled drug delivery systems, acting as a protective depot for the drug, has expanded significantly over the last decades. Among these, injectable hydrogels have emerged as a promising platform, especially in view of the rise of biologicals as therapeutics. Hydrogels are functional, solid-like biomaterials, composed of cross-linked hydrophilic polymers and high water content. Their physical properties, which closely mimic the extracellular matrix, make them suitable for various biomedical applications. This review discusses the different types of hydrogel systems and their self-assembly process, with an emphasis on peptide-based hydrogels. Due to their structural and functional diversity, biocompatibility, synthetic accessibility, and tunability, peptides are regarded as promising and versatile building blocks. A comprehensive overview of the variety of peptide hydrogels is outlined, with β-sheet forming sequences being highlighted. Key factors to consider when using peptide hydrogels as a controlled drug delivery system are reviewed, along with a discussion of the main drug release mechanisms and the emerging trend towards affinity-based systems to further refine drug release profiles.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676027","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":"Identification and synthesis of a long-chain antimicrobial peptide from the venom of the Liocheles australasiae scorpion","authors":"Masahiro Miyashita, Shoichi Sakai, Ryota Okabe, Sayaka Kawai, Takumi Kishimoto, Atsushi Kitanaka, Naoya Mitani, Yoshiaki Nakagawa","doi":"10.1002/psc.3661","DOIUrl":"10.1002/psc.3661","url":null,"abstract":"<p>Scorpion venom contains linear peptides without disulfide bonds in addition to peptides with disulfide bonds. Many such linear peptides have an amphiphilic α-helical structure, often with antimicrobial activity and can be classified into three groups based on their molecular size. Among them, long-chain antimicrobial peptides consisting of more than 40 residues have not been thoroughly studied due to the difficulty of synthesizing them. We have previously reported a transcriptome analysis of the venom gland of <i>Liocheles australasiae</i> that revealed precursor sequences of long-chain antimicrobial peptides. In the study reported here, we identified the mature structure of one such long-chain antimicrobial peptide, LaCT1, which we synthesized using chemical ligation to confirm its structure and evaluate its biological activities. The result showed that LaCT1 exhibited significant antimicrobial activity. In addition, we identified its partial peptides consisting of an N- or C-terminal region, which may be generated by enzymatic cleavage in the venom. Among them, only the peptide containing the N-terminal half region was active. LaCT1 also not only showed insecticidal activity but also synergistically enhanced the effects of another insecticidal peptide identified in <i>L. australasiae</i> venom as well. These results provide insights into the role of antimicrobial peptides in scorpion venom.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568504","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":"Editorial for the Special Collection “Women in Peptide Science”","authors":"Anna Maria Papini, Ines Neundorf, Diana Imhof","doi":"10.1002/psc.3659","DOIUrl":"10.1002/psc.3659","url":null,"abstract":"","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522220","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}
Michela Bollati, Elettra Fasola, Stefano Pieraccini, Francesca Freddi, Paolo Cocomazzi, Francesco Oliva, Merlin Klußmann, Angelo Maspero, Umberto Piarulli, Silvia Ferrara, Sara Pellegrino, Giovanni Bertoni, Silvia Gazzola
{"title":"Impairing protein–protein interactions in an essential tRNA modification complex: An innovative antimicrobial strategy against Pseudomonas aeruginosa","authors":"Michela Bollati, Elettra Fasola, Stefano Pieraccini, Francesca Freddi, Paolo Cocomazzi, Francesco Oliva, Merlin Klußmann, Angelo Maspero, Umberto Piarulli, Silvia Ferrara, Sara Pellegrino, Giovanni Bertoni, Silvia Gazzola","doi":"10.1002/psc.3658","DOIUrl":"10.1002/psc.3658","url":null,"abstract":"<p>Protein–protein interactions (PPIs) have been recognized as a promising target for the development of new drugs, as proved by the growing number of PPI modulators reaching clinical trials. In this context, peptides represent a valid alternative to small molecules, owing to their unique ability to mimic the target protein structure and interact with wider surface areas. Among the possible fields of interest, bacterial PPIs represent an attractive target to face the urgent necessity to fight antibiotic resistance. Growing attention has been paid to the YgjD/YeaZ/YjeE complex responsible for the essential t<sup>6</sup>A<sub>37</sub> tRNA modification in bacteria. We previously identified an α-helix on the surface of <i>Pseudomonas aeruginosa</i> YeaZ, crucial for the YeaZ-YeaZ homodimer formation and the conserved YeaZ-YgjD interactions. Herein, we present our studies for impairing the PPIs involved in the formation of the YeaZ dimers through synthetic peptide derivatives of this helical moiety, both <i>in vitro</i> with purified components and on <i>P. aeruginosa</i> cells. Our results proved the possibility of targeting those PPIs which are usually essential for protein functioning and thus are refractory to mutational changes and antibiotic resistance development.</p>","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"31 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468320","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}