Where are peptide ligands of potassium channels sourced from?

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.