6-Arylpyrido[2,3-d]pyrimidines as novel ATP-competitive inhibitors of bacterial D-alanine:D-alanine ligase.
BACKGROUND: ATP-dependent D-alanine:D-alanine ligase (Ddl) is a part of biochemical machinery involved callaway jaws gap wedge 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 a