A transient initiator for polypeptoids post-polymerization α-functionalization via activation of thioester group

Abstract

Here we introduce a post-polymerization modification method of an α-terminal functionalized poly-(N-methyl-glycine), also known as polysarcosine. We utilized 4-(methylthio)phenyl piperidine-4-carboxylate as an initiator for the ring-opening polymerization of N-methyl-glycine-N-carboxyanhydride followed by oxidation of the thioester group to yield an α-terminal reactive 4-(methylsulfonyl)phenyl piperidine-4-carboxylate polymer. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes and model proteins. The new initiator yielded polymers with well-defined molar mass, low dispersity and high end-group fidelity, as observed by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectroscopy. The introduced method could be of great interest for bioconjugation, but requires optimization, especially for protein conjugation.