Модифицированные олигонуклеотиды, содержащие карбоксильную или альдегидную группу, и получение конъюгатов на их основе тема автореферата и диссертации по химии, 02.00.10 ВАК РФ

1. УСЛОВНЫЕ СОКРАЩЕНИЯ

2. ВВЕДЕНИЕ

3. ОЛИГОНУКЛЕОТИДЫ, СОДЕРЖАЩИЕ РЕАКЦИОННОСПОСОБНЫЕ ЭЛЕКТРОФИЛЬНЫЕ ГРУППИРОВКИ (Литературный обзор)

3.1. Введение

3.2. Синтез олигонуклеотидов, содержащих 5'-концевую карбоксильную или альдегидную группу

3.3. Синтез олигонуклеотидов, содержащих З'-концевую карбоксильную или альдегидную группу

3.4. Синтез олигонуклеотидов, содержащих карбоксильную или альдегидную группу в середине цепи

3.4.1. Олигонуклеотиды, содержащие карбоксильную или альдегидную группу в гетероциклическом основании

3.4.2. Олигонуклеотиды, содержащие карбоксильную или альдегидную группу в составе звена ненукпеотидной природы

3.4.3. Олигонуклеотиды, содержащие альдегидную группу в составе апуринового сайта

3.4.4. Олигонуклеотиды, содержащие карбоксильную или альдегидную группу в 2'-положении углеводного фрагмента

6. ВЫВОДЫ

1. Впервые синтезированы модифицированные олигодезоксирибонуклеотиды, содержащие карбоксильную или альдегидную функции в 2'-положении углеводного фрагмента.

2. Разработаны эффективные схемы синтеза мономерных компонентов автоматического олигонуклеотидного синтеза - амидофосфитных производных А/6-бензоил-9-(2-0-метилоксикарбонилметил-5-0-диметокситритил-р-0-рибо-фуранозил)аденина, 1-(2-0-аллилоксикарбонилметил-5-0-диметокситритил-р-0-рибофуранозил)урацила, 1-(2-0-бензилоксикарбонилметил-5-0-ди-метокситритил-р-0-рибофуранозил)урацила, 1-(2-0-(2,3-дибензоилокси-пропил)-5-0-диметокситритил-р-0-рибофуранозил)урацила.

3. Продемонстрирована высокая реакционная способность электрофильных группировок полученных модифицированных олигодезоксирибонуклеотидов в реакциях с нуклеофильными агентами.

4. Предложен и синтезирован мономерный компонент для введения карбоксильной функции на 5'-конец олигонуклеотидной цепи - 0-[1-метил-3-(2-хлортритилоксикарбонил)пропил]-0'-2-цианэтил-Л/,Л/-диизопропиламидо-фосфит.

5. Разработан эффективный метод твердофазного синтеза олигонуклеотидных конъюгатов, основанный на использовании олигодезоксирибонуклеотидов, содержащих 5-концевую карбоксильную функцию.

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