Synthesis and antimicrobial activity of truncated fragments and analogs of citropin 1.1: The solution structure of the SDS micelle-bound citropin-like peptides

Citropin 1.1 is a basic, highly hydrophobic, 16-amino acid peptide (GLFDVIKKVASVIGGL-NH2), 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)[Ala4]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 H2O/SDS-d25 solution, citropin 1.1 adopts two α-helices in the fragments 4-7 and 10-16, respectively, separated by βIV-turn at position 8, 9. The (1-12)citropin adopts an α-helical structure along the entire backbone. In turn, (1-13)[Ala4]citropin demonstrates the tendency to adopt only a short α-helix in the middle part. Moreover, the conversion of α-helix to 310-helix has been noticed in about 30% of conformations. The 310-helical units could be thermodynamic intermediates during folding and unfolding of the α-helical segment of the peptide.