title: Spectral and biological evaluation of a synthetic antimicrobial peptide derived from 1-aminocyclohexane carboxylic acid.
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 43μM. 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-(1)H 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.
authors: US Army Dental and Trauma Research Detachment, Institute of Surgical Research, 3650 Chambers Pass, Building 3610, Fort Sam Houston, TX 78234, USA.
authors: J J
authors: JJ
authors: Abercrombie
authors: US Army Dental and Trauma Research Detachment, Institute of Surgical Research, 3650 Chambers Pass, Building 3610, Fort Sam Houston, TX 78234, USA.
authors: Kai P
authors: KP
authors: Leung
authors: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA.
authors: Hanbo
authors: H
authors: Chai
authors: Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA. Electronic address: rhicks@gru.edu.
authors: Rickey P
authors: RP
authors: Hicks
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000598:Amino Acids, Cyclic / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D021902:Enterobacter aerogenes / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000598:Amino Acids, Cyclic; D023181:Antimicrobial Cationic Peptides; D003509:Cyclohexanecarboxylic Acids; C014966:1-aminocyclohexanecarboxylic acid
keywords: 1-Aminocyclohexane carboxylic acid; 2D-NMR; A. baumannii; Antimicrobial peptide; CD; Enterobacter aerogenes; Enterococcus faecium; K. pneumoniae; Lipopolysaccharides; Liposomes; P. aeruginosa; S. aureus