Bioactive peptides derived from the Limulus anti-lipopolysaccharide factor: structure-activity relationships and formation of mixed peptide/lipid complexes.
The design of peptides that would interact and neutralise bacterial endotoxins or LPS could have benefited from the analysis of comparative structure-activity relationships among close-related analogues. Here, we present a comparative structural characterisation of selected peptides derived from the LALF obtained by single-amino-acid replacement, which differ in biological activity. The peptides were characterised in solution using nuclear magnetic resonance, circular dichroism and fluorescence spectroscopies. Membrane mimetic peptide interactions were studied using fluorescence resonance energy transfer with the aid of extrinsic fluorescent probes that allowed the identification of mixed peptide/lipid complexes.
Mora
Puig
P
Department of Medicinal Chemistry. Centro de Investigación Príncipe Felipe. Avda Autopista del Saler, 16. E-46013 Valencia, Spain.
López De La Paz
Manuela
M
Pérez-Payá
Enrique
E
D019943:Amino Acid Substitution; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D002462:Cell Membrane / Q000737:chemistry; D002942:Circular Dichroism / Q000379:methods; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007447:Invertebrate Hormones / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D046911:Macromolecular Substances / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D012996:Solutions / Q000737:chemistry; D013050:Spectrometry, Fluorescence / Q000379:methods; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D060829:Arthropod Proteins; D005456:Fluorescent Dyes; D007447:Invertebrate Hormones; C499147:LALF-14 peptide; D008055:Lipids; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D010456:Peptides, Cyclic; D012996:Solutions; D014409:Tumor Necrosis Factor-alpha; C034705:antilipopolysaccharide factor (Limulus)