SOLUTION STRUCTURE OF THE ANTIMICROBIAL PEPTIDE RANALEXIN AND A STUDYOF ITS INTERACTION WITH PERDEUTERATED DODECYLPHOSPHOCHOLINE MICELLES

Ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana catesbeiana displays antimicrobial activity. This peptide contai ns two cysteine residues in positions 14 and 20 linked by a disulphide bridge. Ranalexin was chemically synthesised and close antimicrobial activities were measured for the reduced and oxidised forms. The solut ion structure of ranalexin was determined by using circular dichroism, proton NMR spectroscopy and molecular modelling techniques. The reduc ed and oxidised forms of ranalexin are mainly unstructured in water bu t display an alpha-helical structure spanning residues 8-15 and 8-17, respectively, in a trifluoroethanol/water mixture (3:7, by vol.). Rana lexin was found to interact with micelles of dodecylphosphocholine and to adopt a similar helical structure. Moreover, slow-exchanging amide protons located on the same side of the helix suggest that the hydrop hobic face of the helix lies on the micelle surface. Hydrophobic resid ues of the poorly structured N-terminal part which are important for t he biological activity an also involved in the interaction with micell es. Taken together, the results suggest that the disulphide bond does not strongly affect either the conformation or the antimicrobial activ ity of ranalexin.