Фонд поддержки проектов Национальной технологической инициативы
Екатеринбург, Россия
Уральский государственный лесотехнический университет
Екатеринбург, Свердловская область, Россия
Пептиды являются потенциально перспективными аналогами синтетических лекарственных препаратов для лечения гиперурикемии. Цель исследования – идентифицировать устойчивые аминокислотные паттерны, обуславливающие ингибирующую ксантиноксидазную активность пептидов, предложить на их основе новые антигиперурикемические пептиды с доказанной посредством использования методологии пред иктивной аналитики in silico эффективностью. Объектами исследования являлись пептиды, обладающие ингибирующей ксантиноксидазной активностью. В работе применялась авторская программа поиска, идентификации и количественной оценки повторяющихся сочетаний аминокислотных остатков в целевых пептидных последовательностях. Проводили оценку физико-химических и фармакокинетических свойств, ингибирующей ксантиноксидазной активности, общей и целевой биологической активности, а также токсичности идентифицированных пептидов. Количество аминокислот в цепи, изоэлектрическая точка, заряд при нейтральном pH, молекулярная масса пептидов и индекс гидрофобности были рассчитаны теоретически. Идентифицированы аминокислотные паттерны, ответственные за процесс ингибирования фермента ксантиноксидазы, сгенерированы новые пептидные последовательности. Идентифицированы 49 нетоксичных пептидов с различной длиной аминокислотной последовательности, обладающих потенциально высокой антимикробной и ингибирующей активностью в отношении целевых мишеней лекарственных препаратов, используемых при гиперурикемии и сахарном диабете 2 типа. Пептиды охарактеризовали как низкомолекулярные соединения гидрофильной (преимущественно) и гидрофобной природы длиной от 4 до 7 аминокислот, содержащие в структуре преимущественно аминокислотные остатки пролина, триптофана и фенилаланина со средней молекулярной массой 723 Да и отрицательным зарядом. Результаты данного исследования являются важным шагом в понимании молекулярных механизмов ингибирования фермента ксантиноксидазы и открывают новые перспективы для разработки антигиперурикемических пептидных препаратов.
Пептиды, гиперурикемия, ингибиторы ксантиноксидазы, аминокислотные паттерны, IC50
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