Protein and Peptide Letters最新文献

{"title":"Optimized Deep Knowledge Distillation Framework for Large-Scale Virus-Host Protein Interaction Prediction.","authors":"Farzad Zandi, Parvaneh Mansouri","doi":"10.1016/j.ppl.2026.10.001","DOIUrl":"https://doi.org/10.1016/j.ppl.2026.10.001","url":null,"abstract":"<p><strong>Background: </strong>In a rapidly evolving viral landscape, understanding virus-host protein interactions (VHPIs) is essential to elucidate viral infection mechanisms and support the development of effective therapeutic strategies. Accurate computational Prediction of VHPIs remains challenging because of the complexity and high dimensionality of protein sequence and functional representations.</p><p><strong>Methods: </strong>We propose a Knowledge Distillation framework for pairwise VHPI prediction that integrates three teacher networks with a hybrid student architecture. Protein characteristics were represented using Conjoint Triad (CT), Dipeptide Composition (DC), Dipeptide Deviation from Expected Mean (DDE), Pseudo-Amino Acid Composition (PseAAC), amino acid encoding, and Gene Ontology (GO) features. We used tuned Monte Carlo ISUD for feature selection and compared it with five alternative approaches: PCA, MCFS, NMF, FA, and Optuna. We used an autoencoder to compress the one-hot encoded GO features. We evaluated on 25 randomly balanced datasets and one additional balanced dataset generated using NearMiss. Five-fold cross-validation was performed at the interaction-pair level using an 80:20 training-to-test ratio in each fold. The final configuration consisted of CT features, NearMiss-based data balancing, tuned MC-ISUD feature selection, and the Knowledge Distillation teacher-student framework.</p><p><strong>Results: </strong>The proposed framework achieved 92.91% accuracy and 96.16% AUC-ROC on the evaluated virus-host protein interaction datasets. Comparative experiments demonstrated that the proposed approach outperformed the existing methods considered in this study. These results are specific to the evaluated datasets and pairwise cross-validation design and should not be interpreted as evidence of generalization to completely unseen viral or host proteins.</p><p><strong>Conclusions: </strong>The findings indicate that combining CT-based representation, NearMiss-based data balancing, tuned ISUD feature selection, and Knowledge Distillation provides a computational framework for pairwise VHPI prediction. The predictions should be regarded as computational hypotheses requiring independent experimental validation.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216661","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":"Integrative multi-omics reveals that salvianolic acid a protects against septic liver injury by remodeling amino acid metabolism and redox homeostasis.","authors":"Penghui Li, Yuhua He, Yitao Fan, Xueying Jia, Jingdan Pei, Yingru Liu, Xinyu Gu, Li Li","doi":"10.1016/j.ppl.2026.09.002","DOIUrl":"10.1016/j.ppl.2026.09.002","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced liver injury (SILI) is a severe complication of sepsis associated with high morbidity and mortality. Salvianolic acid A (Sal A), a bioactive phenolic compound isolated from Salvia miltiorrhiza Bunge, exhibits hepatoprotective properties. However, its effects against SILI and underlying molecular mechanisms remain unclear.</p><p><strong>Methods: </strong>A cecal ligation and puncture (CLP)-induced murine sepsis model was established to evaluate the hepatoprotective effects of Sal A. Liver injury was assessed by serum biochemical assays and histopathological examination. Integrated transcriptomic, proteomic, and metabolomic analyses were performed to investigate the molecular mechanisms of Sal A-mediated hepatoprotection.</p><p><strong>Results: </strong>Sal A significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and alleviated hepatic histopathological injury in septic mice. Multi-omics analyses identified 236 differentially expressed genes (DEGs), 590 differentially expressed proteins (DEPs), and 370 differentially expressed metabolites (DEMs). Integrated analyses revealed that Sal A mainly regulated amino acid metabolism, oxidative stress, apoptosis, immune responses, and inflammatory signaling pathways, identifying key regulatory molecules and 37 shared metabolic pathways.</p><p><strong>Conclusions: </strong>Sal A protects against SILI through coordinated regulation of amino acid metabolism, redox homeostasis, apoptosis, immune responses, and inflammatory signaling pathways. Nevertheless, this study has several limitations, including the use of a CLP-induced mouse model, the preventive administration strategy rather than post-onset treatment, and the lack of direct mechanistic validation of key molecular targets. Further studies using clinically relevant therapeutic protocols and targeted experiments are required to confirm the translational potential of Sal A.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"73-85"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025933","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":"Structural and thermodynamic analysis of BRCA1 BRCT variants identified in Middle Eastern breast cancer cohorts.","authors":"Emna Riguene, Angelos Thanassoulas, Aya Alabdulrazzak, Salwa Al-Maraghi, Tala Al-Louzi, Safa Alzneika, Sara Fetais, Noof Al-Khal, Halema AlFarsi, Michail Nomikos","doi":"10.1016/j.ppl.2026.09.001","DOIUrl":"10.1016/j.ppl.2026.09.001","url":null,"abstract":"<p><strong>Background: </strong>BRCA1 is a critical tumor suppressor that maintains genomic integrity through its C-terminal BRCT tandem domain, which mediates phosphoprotein interactions involved in DNA damage response signaling. Missense variants within the BRCT domain may disrupt protein stability and phosphopeptide recognition; however, their functional interpretation is often complicated by conflicting computational predictions and limited experimental evidence. We characterized two Middle Eastern BRCA1 BRCT variants, M1652I and F1662S, identified in Bahraini and Lebanese cohorts, respectively and compared their structural and functional properties with the pathogenic R1699W variant.</p><p><strong>Methods: </strong>The structural stability and binding thermodynamics of wild-type and mutant BRCA1 BRCT domains were evaluated using circular dichroism, thermal denaturation assays and isothermal titration calorimetry (ITC) with phosphorylated BACH1 and CtIP peptides.</p><p><strong>Results: </strong>M1652I and F1662S retained secondary structure and thermal stability comparable to wild-type BRCA1, whereas R1699W exhibited partial destabilization and a reduced melting temperature (ΔT_m = -5.3 °C). ITC demonstrated that M1652I and F1662S preserved near wild-type binding affinities for phosphorylated BACH1 and CtIP peptides, while R1699W showed no detectable phosphopeptide binding under the conditions tested.</p><p><strong>Conclusions: </strong>M1652I and F1662S preserve BRCT structural integrity and phosphopeptide recognition, supporting a likely benign functional effect on BRCA1 BRCT-mediated interactions. These findings highlight the value of experimental biophysical characterization for interpreting BRCA1 variants identified in underrepresented populations. A major limitation is the reliance on in vitro biophysical assays; therefore, additional cellular and in vivo functional studies are required to confirm the biological consequences of these variants.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":"64-72"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888334","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":"Heat shock proteins as modulators of cardiovascular health and disease: From cellular stress to clinical targets.","authors":"Niloofar Naderi, Azam Bolhassani, Fatemeh Pirani","doi":"10.1016/j.ppl.2026.08.002","DOIUrl":"10.1016/j.ppl.2026.08.002","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is a result of complex pathophysiological processes affecting the heart and blood vessels. Heat shock proteins (HSPs) are evolutionarily conserved molecular chaperones that play key roles in maintaining protein homeostasis and cell survival under various stress conditions. Studies have shown the role of HSPs in diseases, including autoimmune disorders, liver, pancreatic, cancer, diabetes, and kidney disorders. Important findings regarding the role of HSPs in cardiovascular diseases include atherosclerosis, ischemic heart disease, atrial fibrillation, cardiomyopathy, heart failure, deep vein thrombosis, and peripheral vascular disease. Several proteins related to HSPs have been identified in various molecular mechanisms, including autophagy, apoptosis, oxidative stress, inflammatory responses, and fibrosis in cardiac disease. This review provides a comprehensive overview of the molecular biology and classification of HSPs, including extracellular HSPs, small HSPs, and co-chaperone molecules. We explored the roles of HSPs in regulated cell death mechanisms and in modulating oxidative stress and inflammatory responses. Furthermore, we demonstrated the pathological and protective roles of specific HSPs by regulating gene expression in response to drugs and cytokines, including geldanamycin and geranylgeranylacetone (GGA), across various cardiovascular conditions, highlighting the potential for HSP-targeted therapies. Promising strategies, including small-molecule inhibitors, inducers, and gene therapies, such as Bcl-2-associated athanogene 3 (BAG3) modulation, are discussed in the context of clinical relevance and therapeutic potential. However, despite promising experimental and clinical evidence, the translational application of HSPs remains limited by their context-dependent biological functions, the lack of standardized biomarker assays, heterogeneous clinical findings, and insufficient large-scale prospective validation. This narrative review was not prospectively registered, and received no external funding. It was conducted by searching PubMed, Scopus, Google scholar and Web of Science for relevant published articles. Understanding the multifaceted roles of HSPs offers new insights into cardiovascular disease mechanisms and paves the way for novel diagnostic and therapeutic approaches.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"34 2","pages":"43-63"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991152","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":"Post-translational modification in cancer: Recent advances and challenges.","authors":"Qingmiao Shi, Nannan Xue, Zhuangzhuang Xue","doi":"10.1016/j.ppl.2026.08.001","DOIUrl":"10.1016/j.ppl.2026.08.001","url":null,"abstract":"","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"34 1","pages":"5-7"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866277","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":"Ubiquitination in hepatocellular carcinoma: mechanisms and therapeutic opportunities.","authors":"Xiaonan Geng, Bing Feng, Xufeng Huang, Wei Wang, Xinjun Hu","doi":"10.1016/j.ppl.2026.07.003","DOIUrl":"10.1016/j.ppl.2026.07.003","url":null,"abstract":"","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"34 1","pages":"1-4"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866385","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":"Efficiency and specificity evaluation of imidazole derivatization reactions for histidine-containing peptides.","authors":"Chenyu Lin, Huaiwang Jia, Meining Xing, Wantao Ying","doi":"10.1016/j.ppl.2026.07.004","DOIUrl":"10.1016/j.ppl.2026.07.004","url":null,"abstract":"<p><strong>Background: </strong>Histidine residues are crucial for protein structure and function, playing key roles in metal coordination, catalysis, and post translational modifications. Comprehensive profiling of functional histidine sites remains technically challenging because of the insufficient chemoselectivity of labeling reagents, and the lack of robust enrichment methods compatible with complex proteomes.</p><p><strong>Methods: </strong>Seven histidine-targeting probes representing three distinct reaction mechanisms were systematically evaluated using a peptide-centric workflow. Reaction conditions were optimized at the peptide level via mass spectrometry, and large-scale assessments of labeling efficiency, site selectivity, and sequence preferences were performed using tryptic digests of HeLa cell lysates.</p><p><strong>Results: </strong>Nucleophilic substitution-based probes preferentially modify histidine in charged microenvironments, whereas nucleophilic addition reagents exhibit broad sequence tolerance and achieve the highest labeling coverage. In contrast, singlet oxygen-mediated probes display increased site-selectivity for C-terminal and dynamically accessible histidine sites, yielding highly confident labeling products with improved biocompatibility. Among all evaluated reagents, acrolein achieved the highest labeling efficiency, while 1-methyl-4-phenyl-1,2,4-triazoline-3,5-dione exhibited superior histidine specificity and compatibility with downstream enrichment strategies.</p><p><strong>Conclusion: </strong>This work provides a comparative framework for histidine-targeted chemical proteomics, establishes optimized labeling and analysis pipelines, and highlights complementary probe reactivities that can be combined with click chemistry for comprehensive histidine profiling in complex biological systems. Nevertheless, the peptide-level study may not fully reflect the reaction in intact proteins due to steric hindrance.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"34 1","pages":"8-18"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866267","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":"Advancing antimicrobial peptides: Mechanisms, design, and applications in the post-antibiotic era.","authors":"Ziba Mirzaee","doi":"10.1016/j.ppl.2026.07.002","DOIUrl":"10.1016/j.ppl.2026.07.002","url":null,"abstract":"<p><p>The rapid emergence of multidrug-resistant and extensively drug-resistant bacteria has intensified the need for alternative antimicrobial strategies in the post-antibiotic era. Antimicrobial peptides (AMPs), as evolutionarily conserved components of innate immunity, have attracted considerable attention due to their broad-spectrum antimicrobial activity, rapid mechanisms of action, and lower propensity for resistance development. This review summarizes the structural diversity, mechanisms of action, and structure-activity relationships (SAR) of AMPs that underpin their biological activity and guide the rational design of next-generation peptide therapeutics. It further discusses recent advances in peptide engineering, peptidomimetic design, machine learning-assisted discovery, innovative production platforms, and the application of CRISPR-Cas genome editing for production host optimization. In addition, the review highlights synergistic therapeutic strategies, current clinical progress, and the expanding applications of AMPs in medicine, food preservation, agriculture, and aquaculture. Despite these advances, challenges including limited stability, potential toxicity, manufacturing costs, and regulatory barriers continue to hinder widespread clinical translation of AMP-based therapeutics. By integrating recent experimental and computational advances with current translational challenges and future perspectives, this review provides a comprehensive overview of the field and highlights key directions for the rational development and clinical translation of next-generation antimicrobial peptides to combat antimicrobial resistance.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"34 1","pages":"19-30"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866208","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":"CD44v6- and VEGFR2-targeting antibody-drug conjugates: Enhancing precision and safety in cancer therapy through a dual-targeting strategy.","authors":"Menghuai Wu, Xuezhe Feng, Wenqiang Huang, Ye Wu, Juanjuan Cui","doi":"10.1016/j.ppl.2026.07.001","DOIUrl":"10.1016/j.ppl.2026.07.001","url":null,"abstract":"<p><strong>Background: </strong>Bispecific antibody-drug conjugates (BsADCs) represent a promising therapeutic strategy to overcome single-target resistance. Here, we developed a dual-targeting BsADC that simultaneously recognizes CD44v6 and VEGFR2.</p><p><strong>Methods: </strong>Spatial configurations were optimized in CHO expression systems. In vitro binding affinities and cytotoxicity were evaluated alongside in vivo anti-tumor efficacy and systemic toxicity in xenograft models.</p><p><strong>Results: </strong>The variant BIWA8-(G4S)₂-DC101-scFv exhibited high stability and an SEC purity of 84.6%. The construct retained antigen-binding affinity and mediated dose-dependent cytotoxicity in vitro. In mouse xenograft models, the dual-targeting BsADC showed potential anti-tumor activity compared to single-target controls, with no overt body weight loss or observable physical toxicity detected during treatment.</p><p><strong>Conclusion: </strong>These findings suggest that the CD44v6/VEGFR2-targeting BsADC represents a potential candidate for targeted cancer therapy.</p><p><strong>Limitations: </strong>High-resolution LC-MS characterization for absolute DAR distribution and long-term toxicity evaluations in non-human primates were not performed in this preliminary work.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"34 1","pages":"31-42"},"PeriodicalIF":2.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866282","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":"Therapeutic Proteins and Peptides of Plant Origin.","authors":"Marcio Viana Ramos","doi":"10.2174/092986653301260401152123","DOIUrl":"https://doi.org/10.2174/092986653301260401152123","url":null,"abstract":"","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":"33 1","pages":"1-2"},"PeriodicalIF":1.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875193","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}