634915-83-6Relevant articles and documents
Synthesis and activity of 5′-uridinyl dipeptide analogues mimicking the amino terminal peptide chain of nucleoside antibiotic mureidomycin A
Howard, Nigel I.,Bugg, Timothy D. H.
, p. 3083 - 3099 (2007/10/03)
A series of 5′-uridinyl dipeptides were synthesised which mimic the amino terminal chain of nucleoside antibiotic mureido omycin A. Aminoacyl-β-alanyl- and aminoacyl-N-methyl-β-alanyl- dipeptides were attached either via an ester linkage to the 5′-hydroxyl of uridine, or via an amide linkage to 5′-amino-5′-deoxyuridine. The most active inhibitor of Escherichia coli phospho-MurNAc-pentapeptide translocase (MraY) was 5′-O-(L-Ala-N-methyl-β-alanyl)-uridine (13l), which also showed 97% enzyme inhibition at 2.35 mM concentration, and showed antibacterial activity at 100 μg/mL concentration against Pseudomonas putida. Both the central N-methyl amide linkage and a 5′ uridine ester linkage were required for highest biological activity. Enzyme inhibition was shown to be competitive with Mg2+. It is proposed that the primary amino terminus of the inhibitor binds in place of the Mg2+ cofactor at the MraY active site, positioned via a cis-N-methyl amide linkage.
