Glycopolypeptide conformations in bioactive block copolymer assemblies influence their nanoscale morphology

We describe the preparation and assembly of glycosylated amphiphilic diblock copolypeptides, where the hydrophilic glycosylated segments adopt either alpha-helical or disordered conformations. In this study, glycosylated amphiphilic diblock copolypeptides were prepared using poly(L-leucine), poly(L), as the hydrophobic segment, and poly(alpha-D-galactopyranosyl-L-lysine), poly(alpha-gal-K), or poly(alpha-D-galactopyranosyl-L-cysteine sulfone), poly(alpha-gal-C-O2), as the hydrophilic segment. The poly(alpha-gal-K) and poly(alpha-gal-C-O2) segments are known to be fully alpha-helical (>90% at 20 degrees C) and fully disordered in water, respectively. We found that block copolypeptides containing galactosylated hydrophilic segments of either alpha-helical or disordered conformation give different assembly morphologies, where the disordered glycopolypeptide segments favor vesicle formation and also present sugar residues that can bind to biological targets.