Synthesis of 5'-methylthio coformycins: specific inhibitors for malarial adenosine deaminase.

ABSTRACT: Transition state theory suggests that enzymatic rate acceleration (kcat/knon) is related to the stabilization of the transition state for a given reaction. Chemically stable analogues of a transition state complex are predicted to convert catalytic energy into binding energy. Because transition state stabilization is a function of catalytic efficiency, differences in substrate specificity can be exploited in the design of tight-binding transition state analogue inhibitors. Coformycin and 2'-deoxycoformycin are natural product transition state analogue inhibitors of adenosine deaminases (ADAs). These compounds mimic the tetrahedral geometry of the ADA transition state and bind with picomolar dissociation constants to enzymes from bovine, human, and protozoan sources. The purine salvage path

SUBMITTER: Tyler PC 

PROVIDER: S-EPMC2522312 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature