UCLA

We have developed a facile method for preparation of ionic copolypeptide vesicles that requires no protecting groups or expensive components. We prepared amphiphilic copolypeptides containing segments of water-soluble methionine sulfonium residues. These were derived by aqueous phase, direct alkylation of a fully hydrophobic precursor diblock copolypeptide, poly(L-methionine)65-block-poly(L-leucine0.5-stat-L-phenylalanine0.5)20 (M65[L0.5/F0.5]20), with simple alkylating reagents. Methylation of M65(L0.5/F0.5)20 gave the cationic methyl-methionine sulfonium derivative MM65(L0.5/F0.5)20, and carboxymethylation gave the zwitterionic carboxymethyl-methionine sulfonium derivative MC65(L0.5/F0.5)20. Assembly of MM65(L0.5/F0.5)20 or MC65(L0.5/F0.5)20 in water gave rise to vesicles with average diameters of a few microns, which could then be extruded to nanoscale diameters. While the cationic MM-based vesicles were found to be cytotoxic, the zwitterionic MC-based vesicles were found to possess minimal cytotoxicity.