Mechanistic study of the reaction of thiol-containing enzymes with alpha,beta-unsaturated carbonyl substrates by computation and chemoassays.

ABSTRACT: We investigated the reactions between substituted alpha,beta-unsaturated carbonyl compounds (Michael systems) and thiols by computations as well as chemoassays. The results give insight into variations in the underlying mechanisms as a function of the substitution pattern. This is of interest for the mechanisms of inhibition of the SARS coronavirus main protease (SARS-CoV M(pro)) by etacrynic acid derivatives as well as for the excess toxicity of substituted alpha,beta-unsaturated carbonyl compounds. This study compares possible reaction courses including 1,4-addition followed by a ketonization step, and underscores the importance of a base-catalyzed step for the reactivity of thiol groups in enzymes. Phenyl and methyl substituents at the Michael system decrease the reactivity of the elect

SUBMITTER: Paasche A 

PROVIDER: S-EPMC7162195 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature