Технология PROTAC^® и перспективы ее применения в борьбе с инфекциями

Цели. Описать фармацевтическую технологию направленной деградации белковых молекул (PROTAC^®, PROteolysis TArgeting Chimera), подходы к конструированию молекулы PROTAC^®, методы подбора и синтеза лигандов и линкера, а также применение данной технологии в борьбе с различными заболеваниями и возможные ограничения ее использования.
Результаты. Обзор охватывает 77 источников, в основном за 2020–2023 гг. В обзоре изложен принцип технологии PROTAC^®, который заключается в конструировании химерной молекулы, состоящей из трех фрагментов. Один фрагмент специфически связывается с биомишенью, другой рекрутирует протеолитическую систему клетки-хозяина, а третий связывает их между собой. Описаны направления современного развития технологии, а также возможности и ограничения химерных молекул в борьбе с разными типами инфекционных заболеваний.
Выводы. Показаны перспективы использования технологии PROTAC^® в борьбе с онкологическими, нейродегенеративными, аутоиммунными и инфекционными заболеваниями.

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