6-Arylpyrido[2,3-d]pyrimidines as novel ATP-competitive inhibitors of bacterial D-alanine:D-alanine ligase.

ABSTRACT:

Background

ATP-dependent D-alanine:D-alanine ligase (Ddl) is a part of biochemical machinery involved in peptidoglycan biosynthesis, as it catalyzes the formation of the terminal D-ala-D-ala dipeptide of the peptidoglycan precursor UDPMurNAc-pentapeptide. Inhibition of Ddl prevents bacterial growth, which makes this enzyme an attractive and viable target in the urgent search of novel effective antimicrobial drugs. To address the problem of a relentless increase in resistance to known antimicrobial agents we focused our attention to discovery of novel ATP-competitive inhibitors of Ddl.

Methodology/principal findings

Encouraged by recent successful attempts to find selective ATP-competitive inhibitors of bacterial enzymes we designed, synthesized and evaluated a library of 6-a

SUBMITTER: Skedelj V 

PROVIDER: S-EPMC3410885 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature