D-alanyl–D-alanine or D-alanyl–D-lactate terminus of peptidoglycan

The D-alanyl–D-alanine terminus is the typical end of the peptide chains attached to the muramyl sugar residues in bacterial peptidoglycan, serving as the substrate for cross-linking by transpeptidases during cell wall assembly. Vancomycin and related antibiotics bind specifically to D-Ala–D-Ala motifs, thereby inhibiting cell wall synthesis and causing bacterial death. Some bacteria develop resistance by producing peptidoglycan precursors ending in D-alanyl–D-lactate, which reduces antibiotic binding affinity and impedes the antibiotic’s mechanism of action[9]. These peptide termini are critical determinants for bacterial susceptibility to glycopeptide antibiotics and play a central role in both the structure and pathophysiology of bacterial infections[5][9]. This target does not correspond to a protein, receptor, enzyme, or transporter, but rather a structural motif in the bacterial cell wall, which is nonetheless a fundamental therapeutic target for antibiotics[9].

Other names

D-Ala-D-Ala terminusD-Ala-D-Lac terminuspeptidoglycan peptide terminusvancomycin-binding site

Glycopeptide antibiotics such as vancomycin directly bind to the D-Ala–D-Ala peptide of peptidoglycan precursors, blocking cross-linking required for cell wall synthesis and leading to bacterial cell death. Some bacteria acquire resistance by exchanging D-Ala–D-Ala with D-Ala–D-Lac, which reduces vancomycin binding affinity and confers resistance[9].