Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia.
Molecular Physiology Laboratory, Infection and Immunity Theme, Lee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore.
Neuropharmacology. 2017 Dec;127:124-138. doi: 10.1016/j.neuropharm.2017.07.002. Epub 2017 Jul 5.
Voltage-gated potassium channels play a key role in human physiology and pathology. Reflecting their importance, numerous channelopathies have been characterised that arise from mutations in these channels or from autoimmune attack on the channels. Voltage-gated potassium channels are also the target of a broad range of peptide toxins from venomous organisms, including sea anemones, scorpions, spiders, snakes and cone snails; many of these peptides bind to the channels with high potency and selectivity. In this review we describe the various classes of peptide toxins that block these channels and illustrate the broad range of three-dimensional structures that support channel blockade. The therapeutic opportunities afforded by these peptides are also highlighted. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.'
电压门控钾通道在人类生理学和病理学中发挥着关键作用。反映其重要性的是,已经确定了许多由这些通道的突变或自身免疫攻击引起的通道病。电压门控钾通道也是来自有毒生物体(包括海葵、蝎子、蜘蛛、蛇和锥形蜗牛)的广泛肽毒素的靶标;这些肽中的许多都具有高亲和力和选择性与通道结合。在这篇综述中,我们描述了阻断这些通道的各种肽毒素,并说明了支持通道阻断的广泛的三维结构。还强调了这些肽带来的治疗机会。本文是主题为“毒液衍生肽作为药理学工具”的特刊的一部分。