Polypeptide End-Capping Using Functionalized Isocyanates: Preparation of Pentablock Copolymers

The use of electrophiles (isocyanates, isothiocyanates, acid chlorides) to cap the N-terminal ends of polypeptides and the use of isocyanates to prepare poly(γ-benzyl- l -glutamate)- b -(nonpeptide polymer) block copolymers are described. This chemistry was also used to prepare poly(ethylene glycol)- b -poly(γ-benzyl- l -glutamate)- b -( polymer )- b -poly(γ-benzyl- l -glutamate)- b -poly(ethylene glycol) pentablock copolymers, where polymer = polyoctenamer, poly(ethylene glycol), or poly(dimethylsiloxane). These α,ω-diamino-terminated polymers ( polymer ) were used to prepare difunctional macroinitiators for the living polymerization of γ-benzyl- l -glutamic acid- N -carboxyanhydride (Glu NCA) to form triblock copolymers that were subsequently capped with isocyanate terminated poly(ethylene glycol) to give the pentablock copolymers. These methods allow the facile functionalization of the N-terminal ends of polypeptides from NCA polymerizations. They also were shown to allow the controlled preparation of “rod−coil” polypeptide−(nonpeptide polymer) multiblock architectures with good control over the chain lengths of the domains and without formation of homopolypeptide contaminants.