Poly(ethylene glycol-co-allyl glycidyl ether)s: a PEG-based modular synthetic platform for multiple bioconjugation

A series of random copolymers comprising ethylene oxide (EO) and 0-100% allyl glycidyl ether (AGE) has been prepared by anionic ring-opening polymerization with molecular weights between 5000 and 13,600 g/mol and polydispersity indices in the range of 1.04-1.19. As key for the homogeneity of the PEG conjugates, real-time 1H NMR polymerization kinetics, 13C NMR analysis of triad sequence distribution, and analysis of the thermal behavior by differential scanning calorimetry (DSC) revealed a distinctive random copolymer structure. Via thiol-ene coupling (TEC), showing mainly "click" characteristics and nearly quantitative yields, PEG derivatives with multiple amino, carboxy, or hydroxy functionalities have been prepared, providing suitable reactivities for further attachment. Without further modification, P(EO-co-AGE)s were conjugated with cysteine or the tripeptide glutathione (GSH) via TEC, resulting in well-defined hybrid materials with multiple peptide units conjugated to the PEG backbone. The results demonstrate superior loading capacity of the copolymers in comparison to the PEG homopolymer.