{"title":"Where are peptide ligands of potassium channels sourced from?","authors":"Alexey I Kuzmenkov, Alexander A Vassilevski","doi":"10.1016/j.molpha.2026.100135","DOIUrl":null,"url":null,"abstract":"<p><p>Potassium (K<sup>+</sup>) channels are targeted by a wide range of chemical and biological substances, with peptide ligands standing out due to their exceptional affinity and selectivity. Although most of these molecules belong to venom-derived compounds, novel ligands from various less investigated or less popular sources are being discovered. Application of polypeptides is not restricted to fundamental studies and can be expanded to drug discovery, clinical pharmacology, and pharmaceutics. In this report, we offer a concise overview of the diversity of K<sup>+</sup> channel ligands and their sources, briefly summarizing recent developments in the field and providing an outlook. SIGNIFICANCE STATEMENT: This paper provides a concise overview of the diversity of K<sup>+</sup> channel ligands and their natural sources, highlights recent advances, and outlines future directions. Although venom-derived polypeptides remain the main source, growing interest is focused on nonvenomous organisms such as plants and mammals. We also discuss artificial polypeptides developed using mutagenesis, and the potential of machine learning and neural networks as promising tools for further molecular design.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 7","pages":"100135"},"PeriodicalIF":3.0000,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.molpha.2026.100135","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/6/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Potassium (K+) channels are targeted by a wide range of chemical and biological substances, with peptide ligands standing out due to their exceptional affinity and selectivity. Although most of these molecules belong to venom-derived compounds, novel ligands from various less investigated or less popular sources are being discovered. Application of polypeptides is not restricted to fundamental studies and can be expanded to drug discovery, clinical pharmacology, and pharmaceutics. In this report, we offer a concise overview of the diversity of K+ channel ligands and their sources, briefly summarizing recent developments in the field and providing an outlook. SIGNIFICANCE STATEMENT: This paper provides a concise overview of the diversity of K+ channel ligands and their natural sources, highlights recent advances, and outlines future directions. Although venom-derived polypeptides remain the main source, growing interest is focused on nonvenomous organisms such as plants and mammals. We also discuss artificial polypeptides developed using mutagenesis, and the potential of machine learning and neural networks as promising tools for further molecular design.
期刊介绍:
Molecular Pharmacology publishes findings derived from the application of innovative structural biology, biochemistry, biophysics, physiology, genetics, and molecular biology to basic pharmacological problems that provide mechanistic insights that are broadly important for the fields of pharmacology and toxicology. Relevant topics include:
Molecular Signaling / Mechanism of Drug Action
Chemical Biology / Drug Discovery
Structure of Drug-Receptor Complex
Systems Analysis of Drug Action
Drug Transport / Metabolism