title: Synthesis and antimicrobial activity of truncated fragments and analogs of citropin 1.1: The solution structure of the SDS micelle-bound citropin-like peptides.
abstract: Citropin 1.1 is a basic, highly hydrophobic, 16-amino acid peptide (GLFDVIKKVASVIGGL-NH(2)), displaying wide-spectrum antimicrobial activities. In this paper we describe the synthesis and antimicrobial properties of citropin 1.1 and its 18 analogs constituting mostly truncated fragments of citropin 1.1. Moreover, we examined conformational properties of citropin 1.1 and its two analogs, (1-12)citropin and (1-13)[Ala(4)]citropin, using FTIR, CD and NMR spectroscopies. Three-dimensional structures of the peptides were determined using molecular dynamics (MD) simulations with time-averaged (TAV) restraints obtained from NMR spectra measured in micellar concentration of sodium dodecyl sulfate (SDS). Earlier investigations showed that in TFE solution, citropin 1.1 is a single helix all along the backbone. However, this structure is not retained in the presence of SDS micelle. In H(2)O/SDS-d(25) solution, citropin 1.1 adopts two alpha-helices in the fragments 4-7 and 10-16, respectively, separated by betaIV-turn at position 8, 9. The (1-12)citropin adopts an alpha-helical structure along the entire backbone. In turn, (1-13)[Ala(4)]citropin demonstrates the tendency to adopt only a short alpha-helix in the middle part. Moreover, the conversion of alpha-helix to 3(10)-helix has been noticed in about 30% of conformations. The 3(10)-helical units could be thermodynamic intermediates during folding and unfolding of the alpha-helical segment of the peptide.
authors.affiliation: University of Gdańsk, Poland. milka@chem.univ.gda.pl
authors.forename: Emilia
authors.initials: E
authors.lastname: Sikorska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Greber
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
authors.forename: Lukasz
authors.initials: L
authors.lastname: Szultka
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lukasiak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
mesh_terms: D029845:Amphibian Proteins / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D029845:Amphibian Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008823:Micelles; C121829:citropin 1.1 protein, Litoria; D012967:Sodium Dodecyl Sulfate