New derivatives of eremomycin containing 15N or F atoms for NMR study

S. E. Solov'eva, S. S. Printsevskaya, E. N. Olsuf'eva, G. Batta, M. N. Preobrazhenskaya

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

New semisynthetic derivatives of eremomycin containing 15N or F atoms 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 [15N]-amide, p-fluorobenzylamide, p-fluorophenylpiperazide, and 6-N-(p-fluorobenzyl) aminohexylamide. A selective method of [15N]-amidation of carboxyl group of amino acid 3 (AA3) of carboxyeremomycin was developed, and the amide of eremomycin containing [15N] in AA3 amide group near the antibiotic binding pocket was obtained. Carboxyeremomycin bisamides substituted at AA3 and AA7 and containing two atoms of [15N] or F were obtained from carboxyeremomycin and [15N]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)747-754
Number of pages8
JournalRussian Journal of Bioorganic Chemistry
Volume34
Issue number6
DOIs
Publication statusPublished - Nov 1 2008

    Fingerprint

Keywords

  • Eremomycin chemical modification
  • Mechanism of action
  • NMR spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

Cite this

Solov'eva, S. E., Printsevskaya, S. S., Olsuf'eva, E. N., Batta, G., & Preobrazhenskaya, M. N. (2008). New derivatives of eremomycin containing 15N or F atoms for NMR study. Russian Journal of Bioorganic Chemistry, 34(6), 747-754. https://doi.org/10.1134/S1068162008060162