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Titolo:
In vivo processing and antibiotic activity of microcin B17 analogs with varying ring content and altered bisheterocyclic sites
Autore:
Roy, RS; Kelleher, NL; Milne, JC; Walsh, CT;
Indirizzi:
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 em & Mol Pharmacol, Boston, MA 02115 USA
Titolo Testata:
CHEMISTRY & BIOLOGY
fascicolo: 5, volume: 6, anno: 1999,
pagine: 305 - 318
SICI:
1074-5521(199905)6:5<305:IVPAAA>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
INFRARED MULTIPHOTON DISSOCIATION; DNA-GYRASE INHIBITOR; DIRECTED MUTAGENESIS; MUTATIONAL ANALYSIS; MASS-SPECTROMETRY; ESCHERICHIA-COLI; PEPTIDE; SEQUENCE; REPLICATION; CLEAVAGE;
Keywords:
antibiotic; gyrase; heterocycles; microcin B17; mutagenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Walsh, CT Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 harmacol, Boston, MA 02115 USA
Citazione:
R.S. Roy et al., "In vivo processing and antibiotic activity of microcin B17 analogs with varying ring content and altered bisheterocyclic sites", CHEM BIOL, 6(5), 1999, pp. 305-318

Abstract

Background: The Escherichia coli peptide antibiotic microcin B17 (MccB17) contains four oxazole and four thiazole rings, and inhibits DNA gyrase,The role of individual and tandem pairs of heterocycles in bioactivity has not been determined previously. Results: The two tandem 4,2-bisheterocycles in MccB17 were varied by expression of MccB17 or mutants containing altered sequences at Gly39-Ser40-Cys41 or Gly54-Cys55-Ser56. A mixture of five-nine-ring MccB17 isoforms were separated and quantitated for antibiotic potency. Mutagenesis of the thiazole-oxazole pair significantly affected antibiotic activity compared with the upstream oxazole-thiazole, which might stabilize partially cyclized intermediates against proteolysis. Conclusions: Enzymatic heterocyclization in native MccB17 occurs distributively, Antibiotic activity correlates with the number of rings and is differentially sensitive to both the location and the identity of the 4,2-tandemheterocycle pairs in MccB17. Such tandem heterocycles might be useful pharmacophores in combinatorial libraries.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 22:37:50