Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Glenn A. Marsch, Raymond L. Ward, Michael Colvin, Ken W Turteltaub

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The cooked meat mutagen 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) is metabolized in vivo to electrophilic intermediates that covalently bind to DNA guanines. Here we address the mechanism of PhIP's non-covalent interaction with DNA by using spectroscopic and computational methodologies. NMR methodologies indicated that upon addition of DNA, PhIP aromatic protons underwent a small, 0.11-0.12 p.p.m. upfield shift. DNA phosphorus resonances of non-covalent PhIP - DNA complexes broadened and slightly shifted upfield, while DNA base imino proton resonances shifted slightly downfield relative to DNA alone. UV and fluorescence spectra of PhIP titrated with DNA showed no detectable shifting and hypochromism of absorbance or fluorescence bands. In the presence of DNA, PhIP fluorescence was efficiently quenched by acrylamide, but not by silver ion. Further, the NMR spectra suggest that PhIP is in fast exchange with the DNA, and is slightly specific for adenine-thymine (A-T) sequences. Finally, structural arguments based on quantum chemistry calculations suggested that PhIP and its metabolites are unlikely to intercalate into DNA. These data collectively indicate that PhIP non-covalently binds in a groove of DNA.

Original languageEnglish (US)
Pages (from-to)5408-5415
Number of pages8
JournalNucleic Acids Research
Volume22
Issue number24
StatePublished - Dec 11 1994
Externally publishedYes

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DNA
Fluorescence
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Protons
Thymine
Acrylamide
Mutagens
Guanine
Adenine
Silver
Meat
Phosphorus
Ions

ASJC Scopus subject areas

  • Genetics

Cite this

Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. / Marsch, Glenn A.; Ward, Raymond L.; Colvin, Michael; Turteltaub, Ken W.

In: Nucleic Acids Research, Vol. 22, No. 24, 11.12.1994, p. 5408-5415.

Research output: Contribution to journalArticle

Marsch, Glenn A. ; Ward, Raymond L. ; Colvin, Michael ; Turteltaub, Ken W. / Non-covalent DNA groove-binding by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. In: Nucleic Acids Research. 1994 ; Vol. 22, No. 24. pp. 5408-5415.
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