Abstract
With the increase of antibiotics resistance of bacteria, antimicrobial peptides have been regarded as potential therapeutic agent that could overcome the resistance problem. Pac525 is a short, antimicrobial peptide novel designed in our laboratory with the sequence acetyl-KWRRWVRWI-NH2. It had broad-spectrum antimicrobial activity against Gram-positive, Gram-negative bacteria and some pathogen. Here we use CD, fluorescence and NMR technology to study the structure characteristics of pac525 bound to SDS micelles, a membrane-mimetic environment. It had been found that pac525 adopts an □-helix at residues2-4 and folds a marked amphipathic structure with hydrophobic core flanked by positively charged residues. The hydrophobic core is composed of Trp2, Val6 and Ile9. Other Trp residue, 5 and 8, are exposed to the solvent with different direction. According to the spin-l l experiment results, we can know that pac525 is located inside the SDS micelle with most of its residues but near the surface except the residue Trp5 which is more buried in the micelle. A possible mode for the interaction between pac525 and membrane is that initially the positive charged patch at the N termini is facing and interacting with the negative charged target membrane electrostatically driven. Then rotation of the molecule leads to reorientation of the hydrophobic residues toward the hydrophobic core of the membrane. Finally, the peptide disintegrates the membrane by disrupting the bilayer curvature. Compared pac525 with other Trp-rich antimicrobial peptide, the positive charge and hydrophobic residues distribution is different but a common characteristic is that one or more Trp are part of a hydrophobic core flanked by positive charged residues. If the membrane permeability is its lethal mechanism to bacteria or there is other mechanism that would affect replication or transcription as indolicidin is still unclear and needs more experiment to prove.