INTERACTIONS OF BASIC AMPHIPHILIC PEPTIDES WITH DIMYRISTOYLPHOSPHATIDYLCHOLINE SMALL UNILAMELLAR VESICLES - OPTICAL, NMR, AND ELECTRON-MICROSCOPY STUDIES AND CONFORMATIONAL CALCULATIONS

The interactions of DMPC small unilamellar vesicles with four amphiphi lic polypeptides [(LKKL)n, (LRRL)n, (LKKL)4, and (YKKY)n] have been in vestigated by circular and infrared dichroism, turbidimetry, electron microscopy, and fluorescence, H-1, and P-31 nuclear magnetic resonance spectroscopy. The main results obtained are the following: (1) Well-d efined complexes are formed by the association of one amino acid resid ue with approximately two lipid molecules. (2) In the presence of poly peptides fusions are observed between SUVs when the molar ratio p is l ess than 0.05, and a clearance effect is observed when p is higher tha n 0.05. (3) The anchoring sites of the polypeptides on DMPC molecules are the negative phosphate groups through electrostatic interactions w ith the terminal NH3+ of lysine residues. (4) The polypeptides adopt a n alpha-helical conformation with their axis parallel to the membrane surface. The hydrophobic part of the amphiphilic alpha helix can penet rate the outer lipid leaflet down to the C5 position. (5) Choline meth yl groups are not involved in the interactions between lipid molecules and amino acid residues. (6) Phosphorus atom mobility around the P-O- glycerol bond is strongly reduced whereas that of methylene groups is progressively weakened when going up from C-13 to C1. Finally, using m odeling and energy calculations a model of possible Ac(LKKL)4NHEt-DMPC SUV complexes is presented.