D-alanyl-D-alanine peptide terminus (D-Ala-D-Ala)

The D-alanyl-D-alanine peptide terminus is a carboxy-terminal dipeptide motif found at the end of the stem pentapeptide in peptidoglycan precursors of bacterial cell walls. It is a key structural element essential for peptidoglycan cross-linking during bacterial cell wall biosynthesis. This motif acts as a substrate for transpeptidase enzymes (penicillin-binding proteins) and is the principal binding site for clinically important antibiotic classes such as vancomycin, which binds the terminus and sterically blocks cell wall cross-linking, and β-lactam antibiotics, which target the transpeptidase active site. Modifications of this terminus, such as substitution with D-alanyl-D-lactate, confer high resistance to glycopeptide antibiotics. The D-Ala-D-Ala terminus therefore remains a validated antimicrobial drug target and has no mammalian equivalent, making it highly specific for selective disruption of bacterial pathogens[1][4][6][8].

Other names

D-Ala-D-AlaD-alanyl-D-alanine dipeptidePeptidoglycan precursor terminus

Vancomycin: Binds directly to the D-Ala-D-Ala terminus, blocking access by transpeptidases and inhibiting cell wall synthesis[1][6]. β-lactam antibiotics (including penicillin): Inhibit penicillin-binding proteins that use the D-Ala-D-Ala motif as a substrate, preventing cross-linking of peptidoglycan strands critical for bacterial cell wall integrity[1][4].