Major and minor groove conformations of DNA trimers modified on guanine or adenine by 4-aminobiphenyl: Adenine adducts favor the minor groove

Robert Shapiro, Stephen Ellis, Brian E. Hingerty, Suse Broyde

Research output: Contribution to journalArticle

Abstract

We have studied the conformational effects of 4-aminobiphenyl modification at C-8 of guanine or adenine on double-stranded DNA trimers. We used sequences with the modified purine at the central base pair and all 16 possible neighboring sequences at the outer pairs. Minimized potential energy calculations were carried out using the molecular mechanics program DUPLEX to survey the conformation space of these adducts, using a total of 1280 starting structures both in the modified guanine series and in the modified adenine series. Conformer families in which the bound 4-aminobiphenyl was located in the DNA major groove, and in the minor groove, were located for both adenine and guanine modification. In the modified guanine series, the major and minor groove families were roughly comparable in energy, and the sequence context determined which was more stable in a particular case. In the modified adenine series, however, the minor groove structure was more than 10 kcal/mol more stable than the major groove structure for all sequences. As a result, minor groove adducts provided most of the global minima in the adenine-modified series. This result may be relevant to a previous mutagenesis study [Lasko et al. (1988) J. Biol. Chem. 263, 15429-15435] in which the hot spot of most frequent occurrence was located at an adenine, in the sequence GAT.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalChemical Research in Toxicology
Volume8
Issue number1
StatePublished - 1995

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Nucleic Acid Conformation
Guanine
Adenine
Conformations
DNA
Mutagenesis
Molecular mechanics
Potential energy
Mechanics
Base Pairing
4-biphenylamine

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Major and minor groove conformations of DNA trimers modified on guanine or adenine by 4-aminobiphenyl : Adenine adducts favor the minor groove. / Shapiro, Robert; Ellis, Stephen; Hingerty, Brian E.; Broyde, Suse.

In: Chemical Research in Toxicology, Vol. 8, No. 1, 1995, p. 117-127.

Research output: Contribution to journalArticle

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