Mechanisms of DNA sequence selective alkylation of guanine-N7 positions by nitrogen mustards.
Quantitative determinations were carried out of the relative reaction rates of several nitrogen mustards at various guanine-N7 positions in DNA fragments of known sequence. The findings suggest structural hypotheses of the origins of the reaction selectivities. End-labeled DNA fragments were reacted with nitrogen mustards, and the guanine-N7 alkylation sites were analyzed by gel electrophoresis. Relative reaction intensities were determined by computer analysis of digitized densitometer scans. The differences in reaction intensities at different G's were in part attributable to the effects of nearest neighbor base pairs on the molecular electrostatic potential near the reaction site. Uracil and quinacrine mustards have specific sequence preferences for reaction that differ from other mustards. The nature of the specific sequence preferences were determined and hypotheses are proposed to explain their origin.
Kohn
K W
KW
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD.
Hartley
J A
JA
Mattes
W B
WB
D000478:Alkylation; D001483:Base Sequence; D002412:Cations; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004249:DNA Damage; D006147:Guanine; D009588:Nitrogen Mustard Compounds; D013329:Structure-Activity Relationship
D002412:Cations; D009588:Nitrogen Mustard Compounds; D006147:Guanine