Acyl-D-alanyl-D-alanine terminus of peptidoglycan precursor (D-Ala-D-Ala terminus)

The acyl-D-alanyl-D-alanine terminus of peptidoglycan precursors is the carboxyl-terminal dipeptide sequence of the stem peptide in nascent bacterial peptidoglycan units, specifically found in Gram-positive and Gram-negative bacteria. It serves as the substrate for DD-transpeptidases (penicillin-binding proteins), which catalyze cross-linking essential for cell wall integrity. This motif is the target of β-lactam antibiotics, which mimic the D-Ala-D-Ala structure to bind and inhibit transpeptidase activity, and glycopeptide antibiotics, which physically bind to the motif and prevent cell wall synthesis. Modifications to this terminal group—such as replacement of the terminal D-Ala with D-Lac or D-Ser—confer resistance to glycopeptides by reducing antibiotic binding affinity. This motif is a classic, validated antimicrobial target but is not a receptor, enzyme, or protein—rather, it is a chemical motif critical for bacterial survival and cell division. Drugs acting on this target are foundational in the treatment of bacterial infections, particularly by disrupting the synthesis of the bacterial cell wall.

Other names

D-alanyl-D-alanine terminusAcyl-D-Ala-D-Ala groupPeptidyl-D-Ala-D-Ala extremityD-Ala-D-Ala motif

β-lactams: Covalent acylation of transpeptidase, preventing cross-linking by mimicking the D-Ala-D-Ala substrate. Glycopeptides: Steric blockade of the D-Ala-D-Ala motif, directly inhibiting transpeptidase and glycosyltransferase access.