Synthesis of heterobifunctional polyethylene glycols with azide functionality suitable for “click” chemistry

Abstract

A heterobifunctional polyethylene glycol (PEG) derivative possessing both “click” and electrophilic functionalities was prepared for use in bioconjugation applications. We utilized a dibenzyl-protected amine functional initiator to prepare high purity amino-PEG-alcohol by the polymerization of ethylene oxide. Subsequent chain-end modification of the heterobifunctional PEG afforded the desired N-hydroxy succinimidyl-PEG-azide derivative in 33% overall yield. This PEG derivative allows for versatile bioconjugation chemistry where activated ester chemistry and “click” chemistry can be selectively performed, an area of orthogonal bioconjugation that has not previously been accessible.