Каталитическое расщепление основного белка миелина антителами тема диссертации и автореферата по ВАК РФ 03.00.04, кандидат химических наук Белогуров, Алексей Анатольевич

• Белогуров, Алексей Анатольевич
• кандидат химических наук
• 2008

Оглавление диссертации кандидат химических наук Белогуров, Алексей Анатольевич

оглавление. список сокращений. введение. искусственные каталитические антитела.

АНТИТЕЛА НА АНАЛОГИ ПЕРЕХОДНЫХ СОСТОЯНИЙ РЕАКЦИИ.

ВВЕДЕНИЕ КАТАЛИТИЧЕСКИХ АМИНОКИСЛОТНЫХ ОСТАТКОВ В СВЯЗЫВАЮЩИЙ ЦЕНТР АНТИТЕЛА ПУТЕМ ХИМИЧЕСКОЙ МОДИФИКАЦИИ ИЛИ САЙТ-НАПРАВЛЕННОГО МУТАГЕНЕЗА.

СОЗДАНИЕ АНТИТЕЛ ДЛЯ КАТАЛИЗА ЭНЕРГЕТИЧЕСКИ НЕВЫГОДНЫХ ПРЕВРАЩЕНИЙ.

АНТИИДИОТИПИЧЕСКИЕ АНТИТЕЛА.

ПОЛУЧЕНИЕ АБЗИМОВ ПУТЕМ РЕАКЦИОННОЙ ИММУНИЗАЦИИ.

АБЗИМЫ, СОДЕРЖАЩИЕ КОФАКТОРЫ.

ГРАНИЦЫ ОБЛАСТИ ПРИМЕНЕНИЯ ИНДУЦИРОВАННЫХ АБЗИМОВ. природные каталитические антитела.

КАТАЛИТИЧЕСКИЕ АНТИТЕЛА К ВАЗОАКТИВНОМУ ИНТЕСТИНАЛЬНОМУ ПЕПТИДУ.

КАТАЛИТИЧЕСКИЕ АКТИВНЫЕ ФРАГМЕНТЫ АНТИТЕЛ.

КАТАЛИТИЧЕСКИЕ АНТИТЕЛА К ТИРОГЛОБУЛИНУ.

ПРОТЕОЛИТИЧЕСКИЕ АНТИТЕЛА К ФАКТОРУ VIII СВЕРТЫВАНИЯ КРОВИ.

ДНК-ГИДРОЛИЗУЮЩИЕ АНТИТЕЛА.

КАТАЛИТИЧЕСКИЕ АНТИТЕЛА НЕОБЫЧНОЙ СПЕЦИФИЧНОСТИ.

ПРИРОДНЫЕ КАТАЛИТИЧЕСКИЕ АНТИТЕЛА КАК ЧАСТЬ ИММУННОЙ СИСТЕМЫ.

МЕТОДИЧЕСКИЕ ОСОБЕННОСТИ ИССЛЕДОВАНИЯ ПРИРОДНЫХ КАТАЛИТИЧЕСКИХ АНТИТЕЛ. 37 ОКСИДАЗНАЯ АКТИВНОСТЬ ИММУНОГЛОБУЛИНОВ. рассеянный склероз.

ОБЩАЯ ХАРАКТЕРИСТИКА.

Т-КЛЕТОЧНЫЙ ОТВЕТ В ПАТОГЕНЕЗЕ РАССЕЯННОГО СКЛЕРОЗА.

РОЛЬ В-КЛЕТОЧНОГО ЗВЕНА.

РОЛЬ НАТИВНОГО ИММУННОГО ОТВЕТА. ЗНАЧЕНИЕ TLR.

КРОСС-РЕАКТИВНОСТЬ БАКТЕРИАЛЬНЫХ АНТИГЕНОВ КАК ВОЗМОЖНАЯ ПРИЧИНА

ВОЗНИКНОВЕНИЯ ЗАБОЛЕВАНИЯ.

ПОДХОДЫ К ДИАГНОСТИКЕ И ЛЕЧЕНИЮ РАССЕЯННОГО СКЛЕРОЗА. основной белок миелина. строение, свойства, функции.

МОЛЕКУЛЯРНАЯ ОРГАНИЗАЦИЯ МИЕЛИНА.

ОСНОВНОЙ БЕЛОК МИЕЛИНА, СТРОЕНИЕ, ФИЗИКО-ХИМИЧЕСКИЕ СВОЙСТВА. результаты и обсуждение.

ОПРЕДЕЛЕНИЕ САЙТ-СПЕЦИФИЧНОСТИ ГИДРОЛИЗА ОСНОВНОГО БЕЛКА МИЕЛИНА

АУТОАНТИТЕЛАМИ.

ИССЛЕДОВАНИЕ СУБСТРАТНОЙ СПЕЦИФИЧНОСТИ АНТИ-ОБМ АУТОАНТИТЕЛ НА МОДЕЛЬНЫХ

ПЕПТИДАХ.

КИНЕТИЧЕСКИЕ ИССЛЕДОВАНИЯ ГИДРОЛИЗА ОБМ И EPEEFRET (ОБМ81-ЮЗ).

Заключение диссертации по теме «Биохимия», Белогуров, Алексей Анатольевич

выводы.

1. Определены шесть основных сайтов протеолиза основного белка миелина (ОБМ) под действием аутоантител, выделенных из сыворотки крови пациентов с PC и мышей линии SJL с индуцированным ЕАЕ. Показано, что расщепление молекулы белка по этим сайтам происходит с примерно равной скоростью. Пять сайтов расположены в иммунодоминантных эпитопах белка, а два из пяти локализованы, кроме того, в районе энцефалитогенного пептида основного белка миелина.

2. Получена эпитопная библиотека рекомбинантных фрагментов ОБМ на основе вектора рЕТ-32Ь-СН(+) для исследования субстратной специфичности выделенных абзимов. Показано, что рекомбинантные белки, содержащие энцефалитогенный пептид ОБМ81"103, обладают субстратными свойствами по отношению к исследованным протеолитическим антителам.

3. Охарактеризованы кинетические параметры гидролиза ОБМ и EPeFRET специфичными аутоантителами, выделенными из сывороток крови пациентов с рассеянным склерозом и модельных мышей линии SJL, развивающих экспериментальный аутоиммунный энцефаломиелит (ЕАЕ).

4. Проанализирована связывающая активность аутоантител человека к эпитопной библиотеке ОБМ. Показана возможность дифференциальной диагностики PC и мимикрирующих нейродегенеративных заболеваний.

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