New derivatives of eremomycin containing (15)n or f atoms for NMR study

S. E. Solov'eva, S. S. Printsevskaia, E. N. Olsuf'eva, G. Batta, M. N. Preobrazhenskaia

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Abstract

New semisynthetic derivatives of eremomycin containing (15)N or F atom were obtained for studying the antibiotic-target interaction in intact cells of Gram-positive bacteria by REDOR NMR method. Interaction of the terminal carboxyl group of amino acid 7 (AA7) of eremomycin with amines in the presence of PyBOP and TBTU reagents resulted in the corresponding [(15)N]-amide, p-fluorobenzylamide, p-fluorophenylpiperazide, and 6-N-(p-fluorobenzyl)aminohexylamide. A selective method of [(15)N]-amidation of carboxyl group of amino acid 3 (AA3) of carboxyeremomycin was developed, and the amide of eremomycin containing [(15)N] in AA3 amide group near the antibiotic binding pocket was obtained. Carboxyeremomycin bisamides substituted at AA3 and AA7 and containing two atoms of [(15)N] or F were obtained from carboxyeremomycin and [(15)N]NH4Cl or the corresponding p-fluorobenzylamine hydrochloride in the presence of PyBOP at pH ~8. The Edman degradation of eremomycin p-fluorobenzylamide gave de-(D-MeLeu)-eremomycin p-fluorobenzylamide, a hexapeptide derivative incapable of the antibiotic binding with -D-Ala-D-Ala fragment of growing cell wall peptidoglycan. Among the compounds studied, carboxyeremomycin bis-p-fluorobenzylamide showed the best activity against both the glycopeptides-sensitive and glycopeptides-resistant strains of staphylococci and enterococci.

Original languageEnglish
Pages (from-to)831-839
Number of pages9
JournalBioorganicheskaia khimiia
Volume34
Issue number6
Publication statusPublished - Jan 1 2008

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  • Medicine(all)

Cite this

Solov'eva, S. E., Printsevskaia, S. S., Olsuf'eva, E. N., Batta, G., & Preobrazhenskaia, M. N. (2008). New derivatives of eremomycin containing (15)n or f atoms for NMR study. Bioorganicheskaia khimiia, 34(6), 831-839.