Synthesis of a tight-binding, multisubstrate analog inhibitor of gentamicin acetyltransferase I.

Publisher Website
Google Scholar
Abstract
Gentamicin acetyltransferase I will catalyze acyl transfer from chloroacetylcoenzyme A to form 3-N-chloroacetylgentamicin. This product can be linked to CoA to form a multisubstrate analog by nucleophilic displacement of the Cl by the S of CoA. The analog can be purified by selective binding to cationic and anionic ion exchange resins. Kinetic analysis of a time-dependent onset and reversal of inhibition of gentamicin acetyltransferase I by the purified multisubstrate analog yields an inhibition constant of 5-20 .times. 10-10 M. The inhibitor does not potentiate antibiotic activity against resistant Escherichia coli. The effectiveness of the tight-binding between the enzyme and the multisubstrate analog demonstrates that inhibitors of resistance can be designed and prepared by specific enzymatic synthesis.