Spectral and biological evaluation of a synthetic antimicrobial peptide derived from 1-aminocyclohexane carboxylic acid

J. J. Abercrombie, Kai P. Leung, Hanbo Chai, Rickey P. Hicks

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ac-GF(A6c)G(A6c)K(A6c)G(A6c)F(A6c)G(A6c)GK(A6c)KKKK-amide (A6c = 1-aminocyclohexane carboxylic acid) is a synthetic antimicrobial peptide (AMP) that exhibits in vitro inhibitory activity against drug resistant strains of Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aerogenes, and Enterococcus faecium at concentrations ranging from 10.9 to 43 μM. Spectroscopic investigations were conducted to determine how this AMP interacts with simple membrane model systems in order to provide insight into possible mechanisms of action. CD and 2D-1H NMR experiments indicated this AMP on binding to SDS and DPC micelles adopts conformations with varying percentages of helical and random coil conformers. CD investigations in the presence of three phospholipid SUVs consisting of POPC, 4:1 POPC/POPG, and 60% POPE/21%POPG/19%POPC revealed: (1) The interactions occurring with POPC SUVs have minimal effect on the conformational diversity of the AMP yielding conformations similar to those observed in buffer. (2) The interactions with 4:1 POPC/POPG, and 60% POPE/21%POPG/19%POPC SUVs exhibited a greater influence on the percentage of different conformers contributing to the CD spectra. (3) The presence of a high of percentage of helical conformers was not observed in the presence of SUVs as was the case with micelles. This data indicates that the diversity of surface bound conformations adopted by this AMP are very different from the diversity of conformations adopted by this AMP on insertion into the lipid bilayer. CD spectra of this AMP in the presence of SUVs consisting of LPS isolated from P. aeruginosa, K. pneumoniae and Escherichia coli exhibited characteristics associated with various helical conformations.

Original languageEnglish (US)
Pages (from-to)1341-1347
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number6
DOIs
StatePublished - Mar 15 2015

Fingerprint

Carboxylic Acids
Conformations
Peptides
Klebsiella pneumoniae
Micelles
Pseudomonas aeruginosa
Enterobacter aerogenes
Acinetobacter baumannii
Enterococcus faecium
Lipid bilayers
Lipid Bilayers
Amides
Escherichia coli
Staphylococcus aureus
Phospholipids
Buffers
Nuclear magnetic resonance
Membranes
Pharmaceutical Preparations
1-palmitoyl-2-oleoylphosphatidylcholine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Spectral and biological evaluation of a synthetic antimicrobial peptide derived from 1-aminocyclohexane carboxylic acid. / Abercrombie, J. J.; Leung, Kai P.; Chai, Hanbo; Hicks, Rickey P.

In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 6, 15.03.2015, p. 1341-1347.

Research output: Contribution to journalArticle

Abercrombie, J. J. ; Leung, Kai P. ; Chai, Hanbo ; Hicks, Rickey P. / Spectral and biological evaluation of a synthetic antimicrobial peptide derived from 1-aminocyclohexane carboxylic acid. In: Bioorganic and Medicinal Chemistry. 2015 ; Vol. 23, No. 6. pp. 1341-1347.
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