DalanineDalanine

DalanineDalanine, in common usage, refers to the dipeptide consisting of two D-alanine residues linked by a single peptide bond, often written as D-Ala-D-Ala. It is a recurrent motif in bacterial cell wall chemistry and serves as a standard substrate in studies of peptidoglycan biosynthesis. The term highlights the presence of D-stereochemistry, which is unusually common in bacterial cell walls but rare in human proteins.

In bacterial cell walls, the stem peptide of peptidoglycan frequently ends with the D-Ala-D-Ala dipeptide. D-alanine–D-alanine ligase (Ddl) enzymes catalyze the final step of forming this dipeptide, which is then incorporated into the growing cell wall precursor. The D-Ala-D-Ala terminus is a critical recognition site for certain antibiotics and biosynthetic enzymes involved in cross-linking the cell wall.

Vancomycin and related glycopeptide antibiotics exert their effect by binding specifically to the D-Ala-D-Ala terminus, thereby inhibiting the transglycosylation and transpeptidation steps essential for cell wall cross-linking. Resistance to vancomycin can arise when bacteria substitute D-Ala-D-Ala with D-Ala-D-Lac, reducing binding affinity and compromising antibiotic activity.

In research and synthesis, D-Ala-D-Ala serves as a model substrate for studying antibiotic mechanisms, peptidoglycan biosynthesis, and the design of peptidomimetics with improved stability. It can be produced synthetically or enzymatically and is used to explore the structural requirements of ligand binding to cell wall–synthesizing enzymes.

Notes: D-Ala-D-Ala is distinct from proteins assembled from L-amino acids and is primarily discussed in the context of bacterial physiology and antibiotic interaction.