title: Synthesis and solution structure of the antimicrobial peptide protegrin-1.
abstract: Protegrins are members of a family of five Cys-rich, cationic antimicrobial peptides recently isolated from porcine cells. We have synthesised an 18-amino-acid peptide that corresponds to protegrin-1. After Cys oxidation, the peptide has bactericidal activity against gram-positive and gram-negative bacteria, similar to that described for the natural peptide. The solution structure of protegrin-1 was investigated by means of 1H-NMR spectroscopy in water and in (CD3)2SO, with distance-geometry and simulated-annealing calculations. The C6-C15 and C8-C13 disulfide pattern was determined on the basis of NMR-derived constraints. These two parallel disulfide bridges stabilised a beta-sheet structure which comprised two antiparallel strands (residues 5-9 and 12-16) linked by a distorted beta-turn (residues 9-12). The N-terminus and C-terminus were essentially disordered. The distribution of hydrophobic and hydrophilic residues at the peptide surface was found to be a structural feature shared with tachyplesin-1, a related peptide which displays cytolytic activity, and, to a lesser extent, with mammalian defensins. These findings led us to assume that the distribution pattern could be required for the cytolytic activity of these peptides.
authors.affiliation: Centre de Biochimie Structurale, UMR C9955, U414 INSERM, Faculté de Pharmacie, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Aumelas
authors.forename: M
authors.initials: M
authors.lastname: Mangoni
authors.forename: C
authors.initials: C
authors.lastname: Roumestand
authors.forename: L
authors.initials: L
authors.lastname: Chiche
authors.forename: E
authors.initials: E
authors.lastname: Despaux
authors.forename: G
authors.initials: G
authors.lastname: Grassy
authors.forename: B
authors.initials: B
authors.lastname: Calas
authors.forename: A
authors.initials: A
authors.lastname: Chavanieu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D011506:Proteins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D013552:Swine; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011506:Proteins; D012996:Solutions; C094880:protegrin-1