Synthesis and biochemical study of N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-(alpha,beta-imido)triphosphate (BuPdGMPNHPP): a non-substrate inhibitor of B family DNA polymerases.
BuPdGMPNHPP was synthesized and assayed as a non-incorporable inhibitor of B family DNA polymerases. The derivative was synthesized by preparation of the imidophosphorane of BuPdG followed by reaction with orthophosphate using the imidazolide method. BuPdGMPNHPP inhibited human DNA polymerase alpha and T4 DNA polymerase 10 and 3.5-times more potently than BuPdGTP, respectively, and was not a substrate for either enzyme. BuPdGMPNHPP acts as an active site affinity probe that could find use in co-crystallization trials of B family DNA polymerases.
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655, USA.
J M
JM
Stattel
I
I
Yanachkov
G E
GE
Wright
D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D003848:Deoxyguanine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans
D003848:Deoxyguanine Nucleotides; D004791:Enzyme Inhibitors; C113477:N(2)-(4-n-butylphenyl)-2'--deoxyguanosine 5'-imidotriphosphate; D006165:Guanylyl Imidodiphosphate; D019951:DNA Polymerase beta