Membrane association and contact formation by a synthetic analogue of polymyxin B and its fluorescent derivatives

被引:31
作者
Clausell, A
Rabanal, F
Garcia-Subirats, M
Alsina, MA
Cajal, Y
机构
[1] Univ Barcelona, Dept Phys Chem, Fac Pharm, E-08028 Barcelona, Spain
[2] Univ Barcelona, Dept Organ Chem, E-08028 Barcelona, Spain
关键词
D O I
10.1021/jp0551972
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
sP-B is a synthetic analogue of the natural lipopeptide antibiotic polymyxin B (PxB) that maintains the ability of the parent compound to form vesicle-vesicle contacts and induce lipid exchange. Exchange is selective, and only monoanionic phospholipids such as 1-palmitoyl-2-oleoyl-glycero-sn-3-phosphoglycerol (POPG) are transferred, whereas dianionic phospholipids such as 1-palmitoyl-2-oleoyl-glycero-sn-3-phosphate (POPA) are not, as shown by fluorescence experiments based on the excimer/monomer ratio of pyrene-labeled phospholipids. Synthetic fluorescent analogues of sP-B are used to investigate the peptide position and orientation in the intermembrane contacts: sP-Bw, an analogue that contains (D)-tryptophan ((D)-Trp) instead of the naturally occurring (D)-phenylalanine, and sP-Bpy, incorporating a pyrene group at the N-terminus. Tryptophan fluorescence, anisotropy, and quenching measurements performed with sP-Bw indicate that the peptide binds and inserts in anionic vesicles of POPG and POPA. However, significant differences are seen depending on the lipid composition, as also demonstrated by fluorescence resonance energy transfer (FRET) experiments from Trp to 7-nitro-2-1,3-benzoxadiazol (NBD) groups at the interface. Intermolecular FRET using sP-Bw as the donor and sP-Bpy as the acceptor indicates self-association of the peptide, possibly forming dimers, when bound to POPG vesicles at concentrations that induce the vesicle-vesicle contacts.
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页码:4465 / 4471
页数:7
相关论文
共 29 条
[1]   Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? [J].
Brogden, KA .
NATURE REVIEWS MICROBIOLOGY, 2005, 3 (03) :238-250
[2]   FLUORESCENCE AND LOCATION OF TRYPTOPHAN RESIDUES IN PROTEIN MOLECULES [J].
BURSTEIN, EA ;
VEDENKINA, NS ;
IVKOVA, MN .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1973, 18 (04) :263-279
[3]   Intermembrane molecular contacts by polymyxin B mediate exchange of phospholipids [J].
Cajal, Y ;
Rogers, J ;
Berg, OG ;
Jain, MK .
BIOCHEMISTRY, 1996, 35 (01) :299-308
[4]   Synergism between mellitin and phospholipase A(2) from bee venom: Apparent activation by intervesicle exchange of phospholipids [J].
Cajal, Y ;
Jain, MK .
BIOCHEMISTRY, 1997, 36 (13) :3882-3893
[5]   Specificity for the exchange of phospholipids through polymyxin B mediated intermembrane molecular contacts [J].
Cajal, Y ;
Ghanta, J ;
Easwaran, K ;
Surolia, A ;
Jain, MK .
BIOCHEMISTRY, 1996, 35 (18) :5684-5695
[6]   DIRECT VESICLE-VESICLE EXCHANGE OF PHOSPHOLIPIDS MEDIATED BY POLYMYXIN-B [J].
CAJAL, Y ;
BERG, OG ;
JAIN, MK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 210 (03) :746-752
[7]   Development of antimicrobial agents in the era of new and reemerging infectious diseases and increasing antibiotic resistance [J].
Cassell, GH ;
Mekalanos, J .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (05) :601-605
[8]  
Chávez A, 2001, BIOPOLYMERS, V58, P63, DOI 10.1002/1097-0282(200101)58:1<63::AID-BIP70>3.3.CO
[9]  
2-C
[10]   Synthesis and membrane action of polymyxin B analogues [J].
Clausell, A ;
Rabanal, F ;
Garcia-Subirats, M ;
Alsina, MA ;
Cajal, Y .
LUMINESCENCE, 2005, 20 (03) :117-123