Sequence-defined polypeptide-polymer conjugates utilizing reversible addition fragmentation transfer radical polymerization

Straightforward solid-phase-supported synthesis routes were presented to obtain novel oligopeptide-based reversible addition fragmentation transfer (RAFT) agents. These approaches include the coupling of a functional RAFT agent to a resin-bound peptide and the functionality switch of an oligopeptide ATRP macroinitiator into an oligopeptide transfer agent. The solid-phase-supported methods allowed easy purification of the transfer agents, making difficult column purification steps unnecessary. Well-defined conjugates comprising sequence-defined peptides and synthetic polymers could be accessed by applying RAFT polymerization techniques in combination with the peptide macrotransfer agents. Polymerization reactions of n-butyl acrylate were performed in solution, yielding peptide-polymer conjugates with controllable molecular weight and low polydispersities of around 1.1. The peptide-polymer conjugates were characterized using H-1 NMR spectroscopy and size exclusion chromatography (SEC), while the incorporation of the oligopeptide into the synthetic polymer and the preservation of the chirality were shown by circular dichroism (CD) spectroscopy.