Конструирование и синтез искусственных рибонуклеаз на основе 1, 4-диазабицикло (2.2.2) октана и имидазола

выводы.

1. Сконструированы искусственные рибонуклеазы нового класса, в структурах которых содержатся: имидазолсодержащие функциональные группы, активные в кислотно-основном катализебис-четвертизованный 1,4-диазабицикло[2.2.2]октан, РНКсвязывающая группировка поликатионной природылипофильный углеводородный радикал.

2. Разработана простая универсальная стратегия синтеза предложенных конструкций, позволяющая в широких пределах варьировать как доменную структуру молекулы в целом, так и ее отдельные структурные параметры, влияющие на каталитическую активность: строение каталитического домена, число положительных зарядов в субстрат-связывающем домене, взаиморасположение этих доменов путем изменения длины соединяющего их линкера, липофильность конъюгатов путем изменения размера алифатического углеводородного радикала.

Схемой синтеза предусмотрена также возможность введения в состав молекулы дополнительных функциональных групп.

С использованием разработанных синтетических подходов получены и охарактеризованы 37 новых соединенийвыбор целевых структур определялся возможностью формирования гомологических рядов, в которых конструкции отличаются друг от друга только одним параметром.

3. Предложенные соединения проявили высокую гидролитическую активность в реакции расщепления РНК и сходную специфичность в отношении нуклеотидных последовательностей. Показано, что для проявления высокой рибонуклеазной.

126 активности необходимо наличие в структуре их молекул всех предложенных доменов: имидазолсодержащего каталитического, положительно заряженного РНК-связывающего, а также липофильного радикала. Сравнительный анализ действия синтезированных конструкций внутри гомологических рядов позволил определить оптимальное строение каждого из доменов и их взаимное расположение.

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