Антивирусная и цитотоксическая активности производных нетропсина в культуре клеток Vero, инфицированных вирусами осповакцины и герпеса простого первого типа

Андронова, В.Л.; Гроховский, С.Л.; Суровая, А.Н.; Архипова, В.С.; Гурский, Г.В.; Галегов, Г.А.

Авторы: Андронова В.Л., Гроховский С.Л., Суровая А.Н., Архипова В.С., Гурский Г.В., Галегов Г.А.
Сборник: Доклады Академии наук
Серия: Биохимия, биофизика, молекулярная биология
Том: 422
Год издания: 2008
Место издания: Наука М
Первая страница: 688
Последняя страница: 693
DOI: 10.1134/S0006350910020077
Аннотация: The binding of Pt-bis-Nt and its modified analog Pt*-bis-Nt, which has two additional glycine residues in the linker between two netropsin fragments, to DNA has been studied. The elongation of the linker in the bis-netropsin molecule increases the cytotoxicity and leads to an almost complete loss of the antiherpetic activity of bis-netropsin. The study of the binding of two bis-netropsins to an oligonucleotide duplex containing an AT cluster, which is present at the origin of replication of herpes virus (OriS), revealed significant structuraldifferences between the complexes of bis-netropsins with this DNA oligomer. It was shown by CD spectroscopy that the binding of Pt-bis-Nt in the extended conformation and in hairpin form with the parallel orientation of two bis-netropsin fragments makes a greater contribution to the interaction with the duplex than in the case of Pt*-bis-Nt. At high binding levels, Pt*-bis-Nt binds to the AT cluster in OriS predominantly in the form of associates based on the antiparallel, double-stranded, pyrrolcarboxyamide motif. The interaction of Pt-bis-Ntand Pt*-bis-Nt with a single-stranded oligonuclotide (64 nt) corresponding to the upper strand at the origin of replication of herpes virus (OriS*) was also studied. Substantial differences in the binding of bis-netropsins to OriS* and the thermostability of the resulting complexes were found by CD spectroscopy and UV melting studies. Key words: bis-netropsin, specific recognition in the DNA minor groove, circular dichroism, melting curve, antiherpetic activity
Добавил в систему: Гурский Георгий Валерианович

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