Synthesis of PEG containing cationic block copolymers and their interaction with human serum albumin

Abstract

In this study, we have demonstrated the synthesis of a new series of cationic homopolymers based on 3-methacrylamidopropyl)-trimethylammonium chloride (MAPTAC) and block copolymers based on MAPTAC and poly(ethylene glycol) methyl ether acrylate (PEGMA), with the aim of studying their interactions with human serum albumin (HSA). The homopolymer (PMAPTAC) and its block copolymers containing 69 and 84 mol% PEGMA (PMAPTAC-b-PPEGMA69 and PMAPTAC-b-PPEGMA84 respectively) were prepared by RAFT technique. Interactions between human serum albumin (HSA) and these cationic polymers were studied using fluorescence spectroscopy, along with isothermal titration calorimetry (ITC) and circular dichroism (CD). The fluorescence spectra of these protein–polymer complexes revealed considerable binding affinity between PMAPTAC and HSA. However, the block copolymers exhibited relatively lower binding affinities with HSA that decreased with increase in PEGMA block length. CD studies corroborated the fluorescence data by suggesting the formation of protein–polymer complex that led to considerable loss in the negative ellipticity of HSA resulting from partial unfolding of the polypeptide chain. However, in case of the block copolymers, the presence of PEG partly prevented the perturbation of the polypeptide chain induced by polymer–protein interactions. ITC data suggested that the binding was an entropy-driven process. GdmCl denaturation curves showed increased stability of native HSA in presence of PMAPTAC, indicating higher conformational stability of HSA in presence of the cationic homopolymer.