tailieunhanh - Báo cáo khoa học: Investigations into the ability of an oblique a-helical template to provide the basis for design of an antimicrobial anionic amphiphilic peptide

AP1 (GEQGALAQFGEWL) was shown by theoretical analysis to be an anionic oblique-orientateda-helix former. The peptide exhibited a mono-layer surface area of nm 2 , implying possession of a-helical structure at an air⁄water interface, and Fourier transform infrared spectroscopy (FTIR) showed the peptide to be a-helical (100%) in the presence of vesi-cle mimics of Escherichia colimembranes. | ễFEBS Journal Investigations into the ability of an oblique a-helical template to provide the basis for design of an antimicrobial anionic amphiphilic peptide Sarah R. Dennison1 Leslie H. G. Morton2 Klaus Brandenburg3 Frederick Harris4 and David A. Phoenix1 1 Faculty of Science University of CentralLancashire Preston UK 2 Schoolof NaturalResources University of CentralLancashire Preston UK 3 Forschungszentrum Borstel Leibniz-Center for Medicine and Biosciences Borstel Germany 4 Department of Forensic and Investigative Science University of CentralLancashire Preston UK Keywords anionic antimicrobial a-helical membrane peptide Correspondence D. A. Phoenix Deans Office Faculty of Science University of CentralLancashire Preston PR1 2HE UK Fax 44 1772 892903 Tel 44 1772 893481 E-mail daphoenix@ Received 12 January 2006 revised 12 June 2006 accepted 20 June 2006 doi API GEQGALAQFGEWL was shown by theoretical analysis to be an anionic oblique-orientated a-helix former. The peptide exhibited a monolayer surface area of nm2 implying possession of a-helical structure at an air water interface and Fourier transform infrared spectroscopy FTIR showed the peptide to be a-helical 100 in the presence of vesicle mimics of Escherichia coli membranes. FTIR lipid-phase transition analysis showed the peptide to induce large decreases in the fluidity of these E. coli membrane mimics and Langmuir-Blodgett trough analysis found the peptide to induce large surface pressure changes in monolayer mimics of E. coli membranes mN-m-1 . Analysis of compression isotherms based on mixing enthalpy AH and the Gibbs free energy of mixing AGMix predicted that these monolayers were thermodynamically stable AH and AGMix each negative but were destabilized by the presence of the peptide AH and AGMix each positive . The peptide was found to have a minimum lethal concentration of 3 mM against E. coli and was seen to cause lysis of erythrocytes at 5 mM. In