Toward a greater appreciation of noncovalent chemical/DNA interactions: application of biological and computational approaches.

Abstract:

:Noncovalent DNA interactions, e.g., DNA intercalation and DNA groove-binding, have not been well studied relative to covalent interactions largely due to the inability of predicting and detecting such events in intact cells. We have adapted an in vitro bleomycin amplification method for DNA intercalation for use in cultured V79 Chinese hamster cells and have validated this approach through the use of a three-dimensional DNA computational docking model that quantifies potential strength of DNA intercalative binding based on electrostatics and hydrogen bonding. For many structural classes of molecules, DNA intercalation is necessary but not sufficient for genotoxicity. The present article reviews our progress to date in predicting and confirming noncovalent binding of drugs and other chemicals and in understanding the mechanistic relationship between intercalation and genotoxicity.

journal_name

Environ Mol Mutagen

authors

Snyder RD,Hendry LB

doi

10.1002/em.20096

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

100-5

issue

2-3

eissn

0893-6692

issn

1098-2280

journal_volume

45

pub_type

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