End-Functionalized Phosphorylcholine Methacrylates and their Use in Protein Conjugation

Abstract

Polymer-protein conjugation was performed using N-hydroxysuccinimide and aldehyde-terminated zwitterionic polymers, and the resulting polymer-protein conjugates were characterized by gel electrophoresis and fast protein liquid chromatography. Methacryloyloxyethyl phosphorylcholine (MPC) polymers were prepared by atom transfer radical polymerization in which the requisite functional end-groups for protein conjugation were embedded within the polymerization initiators. These phosphorylcholine polymers were conjugated to lysozyme as a model protein, as well as two therapeutic proteins, granulocyte colony stimulating factor (G-CSF) and erythropoietin (EPO). These MPC polymer-protein conjugates represent alternatives to PEGylated proteins, with the potential to provide improved efficacy in a therapeutic treatment relative to the protein itself.

Structures and Synthesis of Zwitterionic Polymers

“…Similar to the revolutionary changes brought to polyelectrolyte synthesis [106], polyzwitterions have equally profited from this development. RDRP techniques offer direct access to polymers bearing zwitterionic groups with previously unthinkable features, such as predefined molar masses and narrow molar mass distributions [163,[182][183][184][185][186][187][188][189] as well as well-defined functional end groups [61,166,182,[190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208]. Moreover, complex architectures, such as block copolymers [14,[46][47][48]166,167,169,173,187,, graft copolymers [164,213,237,[241][242]…”

Cell membrane-inspired phospholipid polymers for developing medical devices with excellent biointerfaces

“…Because MPC is easily polymerized, numerous MPC polymers having a wide variety of molecular architectures, that is, random copolymers [5], block-type copolymers [6][7][8][9], graft-type copolymers [10][11][12][13], and terminal-functioned polymers [10,14], have been prepared, as shown in figure 2(a). Polymerization of MPC and its derivatives are summarized in this review article [15].…”

PEGylated polymers for medicine: from conjugation to self-assembled systems

“…In 2008, two groups nearly simultaneously reported the synthesis of polyMPC for protein functionalization. 54,55 One report described the synthesis of N-hydroxysuccinimideand benzaldehyde-terminated polyMPC (Fig. 3A), and the conjugation of these polymers to lysozyme (as a model enzyme), and to the therapeutic proteins erythropoietin (EPO) and granulocyte colony stimulating factor (G-CSF).…”

“…3A), and the conjugation of these polymers to lysozyme (as a model enzyme), and to the therapeutic proteins erythropoietin (EPO) and granulocyte colony stimulating factor (G-CSF). 54 Another report described an elegant synthesis of a bis-thiol specific derivative of polyMPC (Fig. 3B) for conjugation to interferon-a2a (IFN).…”