Broad-spectrum peptide inhibitors of aminoglycoside antibiotic resistance enzymes

David D. Boehr, Kari Ann Draker, Kalinka Koteva, Manjeet Bains, Robert E. Hancock, Gerard D. Wright

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The action of aminoglycoside antibiotics is inhibited by chemical modification catalyzed by aminoglycoside inactivating enzymes, which bind these cationic saccharides with active site pockets that contain a preponderance of negatively charged residues. In this study, it was observed that several cationic antimicrobial peptides, representing different structural classes, could serve as inhibitors of such aminoglycoside resistance enzymes. The bovine antimicrobial peptide indolicidin and synthetic analogs appeared to be especially effective against a range of resistance enzymes, inhibiting enzymes belonging to both aminoglycoside phosphotransferase and aminoglycoside acetyltransferase classes, where the mode of action was dependent on the class of antibiotic resistance enzyme. These peptides represent the first example of broad-spectrum inhibitors of aminoglycoside resistance enzymes.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalChemistry and Biology
Volume10
Issue number2
DOIs
StatePublished - Feb 1 2003

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Aminoglycosides
Microbial Drug Resistance
Anti-Bacterial Agents
Peptides
Enzymes
Antimicrobial Cationic Peptides
Kanamycin Kinase
Chemical modification
Catalytic Domain

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Boehr, David D. ; Draker, Kari Ann ; Koteva, Kalinka ; Bains, Manjeet ; Hancock, Robert E. ; Wright, Gerard D. / Broad-spectrum peptide inhibitors of aminoglycoside antibiotic resistance enzymes. In: Chemistry and Biology. 2003 ; Vol. 10, No. 2. pp. 189-196.
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Broad-spectrum peptide inhibitors of aminoglycoside antibiotic resistance enzymes. / Boehr, David D.; Draker, Kari Ann; Koteva, Kalinka; Bains, Manjeet; Hancock, Robert E.; Wright, Gerard D.

In: Chemistry and Biology, Vol. 10, No. 2, 01.02.2003, p. 189-196.

Research output: Contribution to journalArticle

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