Polyisobutylene-based glycopolymers as potent inhibitors for in vitro insulin aggregation.

Abstract

A family of amphiphilic diblock copolymers containing a hydrophobic polyisobutylene (PIB, Mn = 1000 g mol−1) segment and a hydrophilic block with sugar pendants has been synthesized by combining living cationic and reversible addition–fragmentation chain transfer (RAFT) polymerization techniques; to explore their potential in insulin fibrillation inhibition. The glucose content in the hydrophilic segment has been tailor-made from 20 to 57 units to prepare block copolymers. The removal of the acetates from the pendent glucose units resulted in amphiphilic block copolymers that generated micellar aggregates in aqueous media. The treatment of insulin with these block copolymers affected the fibril formation process which was demonstrated using an array of biophysical techniques, namely, thioflavin T (ThT) fluorescence, tyrosine (Tyr) fluorescence, Nile red (NR) fluorescence, isothermal titration calorimetry (ITC), etc. The Tyr fluorescence assay and NR fluorescence study revealed the crucial role of hydrophobic interaction in the inhibition process, whereas ITC measurements confirmed the importance of polar interaction. Thus, the block copolymers exhibit potent inhibition of insulin fibrillation owing to hydrophobic (from PIB segment) and glycosidic cluster effect (from sugar pendant block).