Herpes simplex virus ribonucleotide reductase subunit association inhibitors: the effect and conformation of β-alkylated aspartic acid derivatives

Abstract

Incorporating β-alkylated aspartic acid derivatives into herpes simplex virus ribonucleotide reductase subunit association inhibitors can improve inhibitor potency up to 50 times over the corresponding inhibitors containing an unsubstituted aspartic acid. A combination of NMR studies, conformational analysis, and molecular mechanics calculations suggests that the β-alkyl group improvesinhibitor potency b is provided by a potent conformationally restricted aspartic acid derivative in which the carboxyl group is locked in the putative bioactive conformation.