ИСКУССТВЕННЫЙ ПЕПТИДНЫЙ ЛИГАНД КАЛИЕВОГО КАНАЛА KV1.1 С ВЫСОКОЙ СЕЛЕКТИВНОСТЬЮ
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Ключевые слова

нейротоксин
потенциал-зависимый калиевый канал
блокатор калиевых каналов
яд скорпиона
молекулярное моделирование
молекулярная динамика

Как цитировать

Табакмахер, В. М., Кузьменков, А. И., Гиголаев, А. М., Пиньейро-Жуниор, Э. Л., Пеньёр, С., Ефремов, Р. Г., Титгат, Я., & Василевский, А. А. (2021). ИСКУССТВЕННЫЙ ПЕПТИДНЫЙ ЛИГАНД КАЛИЕВОГО КАНАЛА KV1.1 С ВЫСОКОЙ СЕЛЕКТИВНОСТЬЮ. Российский физиологический журнал им. И. М. Сеченова, 107(4-5), 584–604. https://doi.org/10.31857/S0869813921040130

Аннотация

У млекопитающих обнаружено порядка 40 изоформ потенциал-чувствительных калиевых каналов (KV). Для изучения такого разнообразия KV необходимы вещества, которые способны селективно с ними связываться и изменять их свойства. Ранее мы сообщали о выделении и фармакологической характеристике MeKTx13-3 — пептидного токсина из яда скорпиона Mesobuthus eupeus. Этот токсин обладал высокой аффинностью к ряду KV с незначительной селективностью в отношении изоформы KV1.1. В настоящей работе мы докладываем о получении методом рационального дизайна искусственного производного MeKTx13-3, названного MeKTx13-3_RMRH. Селективность MeKTx13-3_RMRH по отношению к KV1.1 была увеличена на порядок, что делает его одним из самых специфичных лигандов данной изоформы KV. Наконец, используя компьютерное моделирование, мы продемонстрировали, что избирательность нового лиганда KV1.1 может реализовываться за счет специфического положения токсина в комплексе с каналом.

https://doi.org/10.31857/S0869813921040130
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