INTERACTION OF A SYNTHETIC PEPTIDE-BASED ON THE NEUTROPHIL-DERIVED ANTIMICROBIAL PROTEIN CAP37 WITH DIPALMITOYL-PHOSPHATIDYLCHOLINE MEMBRANES

CAP37, a cationic antimicrobial protein of M-r 37 kDa is constitutivel y expressed in human neutrophils. A synthetic peptide, CAP37 P20-44, c orresponding to amino acid residues 20 through 44 of the native CAP37 molecule has been shown to mimic the antimicrobial activity of the nat ive protein. An analog of peptide CAP37 P20-44 was synthesized in whic h the cysteine residues at positions 26 and 42 were replaced with seri ne residues (CAP37 P20-44Ser). This resulted in a peptide that no long er exhibited bactericidal activity. The effect of different concentrat ions of the active CAP37 peptide, CAP37 P20-44, and its inactive analo g, CAP37 P20-44Ser, on artificial lipid membranes composed of dipalmit oyl phosphatidylcholine (DPPC) was studied using small-angle X-ray sca ttering and differential scanning calorimetry, The results indicated t hat CAP37 P20-44 perturbs the periodicity of the lamellar structure as shown by small angle X-ray diffraction, while the effect of the inact ive peptide is not as strong, Differential scanning calorimetry furthe r confirms that CAP37 P20-44 interacts with lipid membranes as indicat ed by increased width of the transition and decreased peak height. Mor eover, it completely abolishes the pretransition temperature of the DP PC membranes, The effect of the inactive peptide, CAP37 P20-44Ser on t he thermotropic properties of DPPC was small. These studies suggest th at CAP37 perturbs the lamellar structure of lipid bilayers and further suggests that the antibiotic action of the molecule may be through it s interactions with the lipid components of the Gram negative bacteria l membrane. (C) 1997 Elsevier Science B.V.