Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, NSW 2522, Australia.
Mar Drugs. 2022 Jul 31;20(8):497. doi: 10.3390/md20080497.
Conopeptides are peptides in the venom of marine cone snails that are used for capturing prey or as a defense against predators. A new cysteine-poor conopeptide, Czon1107, has exhibited non-competitive inhibition with an undefined allosteric mechanism in the human (h) α3β4 nicotinic acetylcholine receptors (nAChRs). In this study, the binding mode of Czon1107 to hα3β4 nAChR was investigated using molecular dynamics simulations coupled with mutagenesis studies of the peptide and electrophysiology studies on heterologous hα3β4 nAChRs. Overall, this study clarifies the structure-activity relationship of Czon1107 and hα3β4 nAChR and provides an important experimental and theoretical basis for the development of new peptide drugs.
芋螺肽是海洋芋螺毒液中的肽类物质，用于捕获猎物或作为防御捕食者的手段。一种新的含半胱氨酸较少的芋螺肽 Czon1107 对人（h）α3β4 烟碱型乙酰胆碱受体（nAChRs）表现出非竞争性抑制作用，其作用机制尚未明确。在这项研究中，使用分子动力学模拟结合对肽的突变研究和对异源 hα3β4 nAChRs 的电生理学研究，研究了 Czon1107 与 hα3β4 nAChR 的结合模式。总的来说，这项研究阐明了 Czon1107 与 hα3β4 nAChR 的结构-活性关系，并为新型肽类药物的开发提供了重要的实验和理论基础。
Zotero 插件
