Бесплатный автореферат и диссертация по биологии на тему

Конструирование и характеристика цитотоксичных гибридных белков на основе генов экзотоксинов Pseudomonas aeruginosa и Corynebacterium diphtheriae

ВАК РФ 03.00.15, Генетика

Заключение Диссертация по теме "Генетика", Здановская, Марина Владимировна

выводы.

1. Сконструированы рекомбинантные плазмиды, содержащие фрагменты гена экзотоксина А (ЕТА) P. aeruginosa. Получены рекомбинантные штаммы Е. coli, в которых происходит образование больших количеств безопасных производных ЕТА, являющихся основой для получения иммунотоксинов Определены особенности структуры гибридных белков, влияющие на уровень их продукции клетками Е. coli.

2. Сконструированы рекомбинантные плазмиды, содержащие фрагменты гена дифтерийного токсина (ДТ) С. diphtheriae . Получены рекомбинантные штаммы Е. coli, в которых происходит образование больших количеств безопасных производных ДТ.

3. Сконструированные производные ЕТА и ДТ очищены и охарактеризованы как компоненты иммунотоксинов и как инструменты для изучения этапов взаимодействия токсинов с эукариотическими клетками.

4. Сконструирован и охарактеризован гибрид между ЕТА и иммуноглобулин-связывающей областью А-белка стафилококка, который могут быть использованы в качестве каталитического компонента иммунотоксинов. Данный гибридный токсин является удобным инструментом для поиска кандидатов на роль адресующего компонента иммунотоксина в коллекциях антител.

5. Показано, что существует негативная корреляция между сродством адресующего компонента к рецептору аг-макроглобулина и токсичностью соответствующего производного токсина. Предложена гипотеза, согласно которой сравнительно низкое сродство ЕТА к рецептору липопротеина низкой плотности (LRP) приводит к тому, что внутри клетки комплекс между ЕТА и рецептором аг-макроглобулина диссоциирует и в результате не транспортируется в лизосому и не деградирует в отличие от других известных лигандов рецептора аг-макроглобулина.

Библиография Диссертация по биологии, кандидата биологических наук, Здановская, Марина Владимировна, Москва

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