Synthesis and activity of 5'-uridinyl dipeptide analogues mimicking the amino terminal peptide chain of nucleoside antibiotic mureidomycin A
UNSPECIFIED. (2003) Synthesis and activity of 5'-uridinyl dipeptide analogues mimicking the amino terminal peptide chain of nucleoside antibiotic mureidomycin A. BIOORGANIC & MEDICINAL CHEMISTRY, 11 (14). pp. 3083-3099. ISSN 0968-0896Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/S0968-0896(03)00207-0
A series of 5'-uridinyl dipeptides were synthesised which mimic the amino terminal chain of nucleoside antibiotic mureido omycin A. Aminoacyl-beta-alanyl- and aminoacyl-N-methyl-beta-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 phosphoMurNAc-pentapeptide translocase (MraY) was 5'-O-((L)-Ala-N-methyl-beta-alanyl)-uridine (131), which also showed 97% enzyme inhibition at 2.35mM concentration, and showed antibacterial activity at 100 mug/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. (C) 2003 Elsevier Science Ltd. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry|
|Journal or Publication Title:||BIOORGANIC & MEDICINAL CHEMISTRY|
|Publisher:||PERGAMON-ELSEVIER SCIENCE LTD|
|Date:||17 July 2003|
|Number of Pages:||17|
|Page Range:||pp. 3083-3099|
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