Химический синтез природных и модифицированных РНК фосфотриэфирным методом тема диссертации и автореферата по ВАК РФ 02.00.10, кандидат химических наук Аралов, Андрей Владимирович

• Аралов, Андрей Владимирович
• кандидат химических наук
• 2011

Оглавление диссертации кандидат химических наук Аралов, Андрей Владимирович

Список сокращений.

Введение.

Защитные группы, используемые в синтезе фрагментов РНК (литературный обзор).

Заключение диссертации по теме «Биоорганическая химия», Аралов, Андрей Владимирович

Выводы

1. Разработана методика введения 2'-0-азидометильной группы в нуклеозиды, позволяющая избежать побочной реакции галогенирования гетероциклических оснований.

2. Разработаны схемы синтеза мономеров, содержащих 2О-азидометильную, 2'-О-{2-азидометил)беизоильную и /У-(2-азидометил)бензоильную группы, для фосфотриэфирного метода синтеза олигорибонуклеотидов на основе 0-нуклеофильного внутримолекулярного катализа. Показано, что использование мономеров, содержащих 2'-О-азидометильную и -/V- (2-азидометил) бснзоильную группы, позволяет эффективно синтезировать фрагменты РНК.

3. Предложены новые фосфорилирующие реагенты, содержащие в своем составе О-нуклеофильную каталитическую 4-метокси-1-оксидо-2-пиколильную Р-защитную группу, использование которых позволяет повысить суммарные выходы мономеров и сократить время их синтеза.

4. Предложен способ введения (4-нитробензилокси) метальной группы в состав рибонуклеозидов, получен 2'-0-(4-ЫВ0М) уридиновый мономер для фосфотриэфирного метода и показана эффективность его использования в синтезе фрагментов РНК.

5. Разработаны схемы синтеза мономеров, содержащих модифицирующую 2 '-О-метоксиметильную группу, использование которых обеспечивает высокоэффективный синтез 2 '-0-модифицированных олигорибонуклеотидов.

6. Исследования по ферментативному расщеплению олигорибонуклеотидов, 2 ' О-модифицированных азидометилыюй или метоксиметильной группами, а также исследования термической стабильности дуплексов, образованных этими аналогами олигорибонуклеотидов с комплементарными НК, позволяют сделать вывод о возможности их применения для различных молекулярно-биологических исследований.

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