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Computational analysis of the effects of site‐specific phosphate alkylation in the DNA oligomer {d‐[GGAATTCC]} 2
Author(s) -
Broido Michelle S.,
Mezei Mihaly
Publication year - 1990
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360290313
Subject(s) - chemistry , alkylation , oligomer , dna , phosphate , stereochemistry , helix (gastropod) , sugar phosphates , organic chemistry , biochemistry , ecology , snail , biology , catalysis
Alkylation of the sugar–phosphate backbone of DNA can result upon exposure to several potent carcinogens, inducing DNA misfunction. In order to assess the structural and energetic changes in DNA helices induced by such alkylation, we have performed AMBER‐based analyses on phosphotriester containing analogues of {d‐[GGAATTCC]} 2 . Fourteen analogues of the nonalkylated oligomer were examined, each bearing a single alkylation of known stereochemistry. Results indicate that although there is minimal effect on the aromatic bases, the presence of a phosphotriester disturbs the sugar–phosphate backbone in complex ways. For most analogues, total minimum energies are lower for the S p ‐alkylations than for the R p ‐alkylations which point directly into the major groove of the helix; however, different energetic contributions follow different, or no, trends in dependence on alkylation site and/or stereochemistry. Where data is available, experimental nmr results agree with the calculations reported here.