D-alanyl-D-alanine-containing peptidoglycan precursor (D-Ala-D-Ala) (D-Ala-D-Ala)

D-alanyl-D-alanine-containing peptidoglycan precursors are essential building blocks in the biosynthesis of the bacterial cell wall, primarily in Gram-positive bacteria (PubChem, CID 14969). These precursors, such as Lipid II, terminate in a D-Ala-D-Ala dipeptide that serves as the substrate for transpeptidase enzymes, also known as penicillin-binding proteins, to create cross-links that provide structural integrity to the peptidoglycan layer (Nature Reviews Microbiology, 2005). This specific dipeptide motif is the primary molecular target for glycopeptide antibiotics, including vancomycin and teicoplanin (StatPearls, 2023). By binding to the D-Ala-D-Ala terminus, these drugs sterically inhibit the assembly of the cell wall, leading to bacterial cell death. Resistance often arises through the modification of this target to D-alanyl-D-lactate or D-alanyl-D-serine, which significantly reduces antibiotic binding affinity (PubMed, PMID 10601204). Understanding this target is crucial for treating severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and other multi-drug resistant organisms.

Other names

D-Ala-D-Ala terminusPeptidoglycan pentapeptideLipid IIUDP-N-acetylmuramyl-pentapeptide

Glycopeptide antibiotics bind to the D-alanyl-D-alanine C-terminus of the peptidoglycan precursors via five hydrogen bonds (StatPearls, 2023). This binding sterically hinders the enzymes transglycosylase and transpeptidase, preventing the polymerization and cross-linking of the peptidoglycan layer, which leads to bacterial cell wall instability and osmotic lysis (Nature Reviews Microbiology, 2005).