Recognition of azole carboxamide nucleobases by DNA polymerases
Abstract
The purpose of this research is to examine the recognition of the azole carboxamide nucleobases by DNA polymerases. The azole carboxamide nucleobases are conformationally flexible, such that rotation about the glycosidic and carboxamide bonds reveals purine or pyrimidine-like configurations. Variation of the electronics of the azole ring (through the placement of nitrogens about the ring) allowed for these nucleobase analogs to be utilized as probes of DNA polymerase recognition. The results indicate that the subtle variations in the electronics of the azole carboxamide cause vastly different recognition by DNA polymerases. These data, in conjunction with high-resolution x-ray crystal structures of DNA polymerases have allowed for many of the key features involved in DNA polymerase recognition to be examined. It was found that minor groove amino acid contacts, nonbonding interactions, 3 ′ to 5′ exonuclease activity, and genetic origin of the DNA polymerase all contribute to the recognition of the azole carboxamide nucleobases.
Degree
Ph.D.
Advisors
Davisson, Purdue University.
Subject Area
Molecular biology
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