D-alanyl-D-alanine terminus of nascent peptidoglycan

The **D-alanyl-D-alanine terminus of nascent peptidoglycan** is a short peptide motif found at the end of the stem peptide in newly synthesized bacterial peptidoglycan precursors. This motif is critical for **bacterial cell wall synthesis**, as it serves as the recognition site for transpeptidase enzymes that cross-link the peptidoglycan strands, giving the cell wall its mechanical strength and protecting bacteria from osmotic lysis[1][4][7]. Some antibiotics, most notably vancomycin, target this terminus by binding directly and blocking cross-linking, leading to inhibition of cell wall synthesis and bacterial death. Alterations of this terminus, such as D-Ala-D-Lac substitution, confer clinically relevant antibiotic resistance[10]. This motif is therefore a major **therapeutic target** in the treatment of bacterial infections and is implicated in the mechanism of action of several critical antibiotic classes.

Other names

D-Ala-D-AlaD-alanyl-D-alanineD-Ala-D-Ala motifD-alanyl-D-alanine moietyterminal D-Ala-D-Ala

Vancomycin and related antibiotics bind directly to the D-Ala-D-Ala terminus, preventing transpeptidase-mediated cross-linking of peptidoglycan and thereby inhibiting cell wall synthesis[10][1]. β-lactam antibiotics mimic the D-Ala-D-Ala structure, irreversibly inactivating transpeptidases that catalyze cross-linking, though they do not directly bind the terminus—rather, they compete at the enzyme’s active site[1].