Biopolym. Cell. 2018; 34(5):387-399.
Биоорганическая химия
Взаимодействие конъюгатов катионного порфирина с имидазофеназином с ДНК-квадруплексом: метод FID и квантово-химическое моделирование
1, 2Дидан Ю. В., 1Ильченко Н. Н., 1Негруцкая В. В., 1Дубей Л. В., 3Рязанова О. А., 1Дубей И. Я.
  1. Институт молекулярной биологии и генетики НАН Украины
    ул. Академика Заболотного, 150, Киев, Украина, 03143
  2. Дельфтский технологический университет
    ван дер Маасвег, Делфт 2629HZ, Нидерланды
  3. Физико-технический институт низких температур им. Б. И. Веркина НАН Украины
    Проспект Науки, 47, Харьков, Украина, 61103

Abstract

Цель. Изучить эффективность трикатионного конъюгата порфирин–имидазо[4,5-b]феназин и его Zn(II) и Mn(III) комплексов как лигандов G-квадруплексной (G4) ДНК. Методы. Метод замещения флуоресцентного интеркалятора (FID) использован для оценки аффинности соединений к модельной дуплексной ДНК и квадруплексу Tel22 при разных значениях ионной силы раствора. Молекулярное моделирование взаимодействия конъюгата с G4-ДНК проведено при помощи вычислений теории функционала плотности (DFT) с использованием функционала M06-2X и базисного набора 6-31G(d). В качестве модели G4 использован гуаниновый октет, стабилизированный ионом K+. Результаты. Определены значения DC50 и константы диссоциации комплексов трех конъюгатов с дуплексной и квадруплексной ДНК. Рассчитаны структуры и энергетические параметры комплексов G-октета с Zn-металлизированным конъюгатом. Выводы. Все соединения проявляют высокую аффинность к квадруплексу Tel22. Увеличение ионной силы приводит к возрастанию селективности к квадруплексной относительно дуплексной ДНК и снижению аффинности связывания лигандов. Структуру комплексов лиганд–G4 определяет прежде всего стекинговое взаимодействие порфиринового фрагмента с G-квартетом, а не интеркаляционное связывание лиганда.
Keywords: G-квадруплекс, лиганды, порфирины, имидазофеназин, FID, DFT

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