Interaction of (2,3)-methylenepenams with penicillin-binding proteins.
AUTOR(ES)
Georgopapadakou, N H
RESUMO
A series of (2,3)-methylenepenams were examined with respect to binding to essential penicillin-binding proteins (PBPs) in Escherichia coli and Staphylococcus aureus. The compounds were also examined with respect to their interaction with Streptomyces strain R61 DD-carboxypeptidase. The alpha isomer of (2,3)-methylene penicillin G bound to PBP 3 of E. coli and other enterobacteria at 0.1 to 10 micrograms/ml. The beta isomer bound to PBP 3 at 100 micrograms/ml. Either isomer bound to PBPs 1b and 2 of E. coli only at 100 micrograms/ml. The alpha, but not the beta, isomer also bound to PBP 2 of S. aureus at 0.1 micrograms/ml. Binding studies with radiolabeled compounds indicated the binding to be covalent and revealed no additional binding proteins. (2,3)-Methylenepenams active against E. coli bound to PBP 3 and induced filamentation. The compounds also inhibited Streptomyces strain R61 DD-carboxypeptidase with apparent 50% inhibitory concentrations as low as 10(-7) M. The two (2,3)-methylene penicillin G isomers bound to the enzyme covalently, most likely at the same site as penicillin G since partial proteolysis after binding radiolabeled compounds produced similar peptide patterns. The bound beta isomer was released with a half-time similar to that of penicillin G (70 min at 30 degrees C), while the alpha isomer was released with a longer half-time (13 h at 30 degrees C). With either isomer, the major release product was phenylacetylglycine, suggesting C-5-C-6 cleavage.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=174873Documentos Relacionados
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