Investigations into the ability of an oblique α-helical template to provide the basis for design of an antimicrobial anionic amphiphilic peptide

被引:18
作者
Dennison, Sarah R.
Morton, Leslie H. G.
Brandenburg, Klaus
Harris, Frederick
Phoenix, David A. [1 ]
机构
[1] Univ Cent Lancashire, Fac Sci, Deans Off, Preston PR1 2HE, Lancs, England
[2] Univ Cent Lancashire, Sch Nat Resources, Preston PR1 2HE, Lancs, England
[3] Leibniz Ctr Med & Biosci, Forschungszentrum Borstel, Borstel, Germany
[4] Univ Cent Lancashire, Dept Forens & Invest Sci, Preston PR1 2HE, Lancs, England
关键词
anionic; antimicrobial; alpha-helical; membrane; peptide;
D O I
10.1111/j.1742-4658.2006.05387.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
AP1 (GEQGALAQFGEWL) was shown by theoretical analysis to be an anionic oblique-orientated alpha-helix former. The peptide exhibited a monolayer surface area of 1.42 nm(2), implying possession of alpha-helical structure at an air/water interface, and Fourier transform infrared spectroscopy (FTIR) showed the peptide to be alpha-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 (4.6 mN.m(-1)). Analysis of compression isotherms based on mixing enthalpy (Delta H) and the Gibbs free energy of mixing (Delta G(Mix)) predicted that these monolayers were thermodynamically stable (Delta H and Delta G(Mix) each negative) but were destabilized by the presence of the peptide (Delta H and Delta G(Mix) 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 combination, these data clearly show that AP1 functions as an anionic alpha-helical antimicrobial peptide and suggest that both its tilted peptide characteristics and the composition of its target membrane are important determinants of its efficacy of action.
引用
收藏
页码:3792 / 3803
页数:12
相关论文
共 60 条
[11]  
DAVIES JT, 1963, INTERFACIAL PHENOMEN
[12]   Strategies for the detection of Escherichia coli O157:H7 in foods [J].
Deisingh, AK ;
Thompson, M .
JOURNAL OF APPLIED MICROBIOLOGY, 2004, 96 (03) :419-429
[13]   Investigations into the membrane interactions of m-calpain domain V [J].
Dennison, SR ;
Dante, S ;
Hauss, T ;
Brandenburg, K ;
Harris, F ;
Phoenix, DA .
BIOPHYSICAL JOURNAL, 2005, 88 (04) :3008-3017
[14]   Amphiphilic α-helical antimicrobial peptides and their structure/function relationships [J].
Dennison, SR ;
Wallace, J ;
Harris, F ;
Phoenix, DA .
PROTEIN AND PEPTIDE LETTERS, 2005, 12 (01) :31-39
[15]   Are oblique orientated α-helices used by antimicrobial peptides for membrane invasion? [J].
Dennison, SR ;
Harris, F ;
Phoenix, DA .
PROTEIN AND PEPTIDE LETTERS, 2005, 12 (01) :27-29
[16]   Factors determining the efficacy of alpha-helical antimicrobial peptides [J].
Dennison, SR ;
Harris, F ;
Phoenix, DA .
PROTEIN AND PEPTIDE LETTERS, 2003, 10 (05) :497-502
[17]   Cationic peptides: Distribution and mechanisms of resistance [J].
Devine, DA ;
Hancock, REW .
CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (09) :703-714
[18]  
Diamond Gill, 2001, Biologist (London), V48, P209
[19]   THE HELICAL HYDROPHOBIC MOMENT - A MEASURE OF THE AMPHIPHILICITY OF A HELIX [J].
EISENBERG, D ;
WEISS, RM ;
TERWILLIGER, TC .
NATURE, 1982, 299 (5881) :371-374
[20]   THE HYDROPHOBIC MOMENT DETECTS PERIODICITY IN PROTEIN HYDROPHOBICITY [J].
EISENBERG, D ;
WEISS, RM ;
TERWILLIGER, TC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (01) :140-144