A guide to maximizing the therapeutic potential of protein–polymer conjugates by rational design

Abstract

Careful planning in the selection of the protein, polymer, conjugation chemistry, and analysis can help maximize the potential of protein–polymer conjugates for therapeutic applications.

A programmable chemical switch based on triggerable Michael acceptors

“…[1][2][3] The signicance of these reactions has been found in a variety of applications, ranging from drug discovery to protein modication, drug delivery, and materials preparation. [4][5][6][7][8][9][10][11][12] Highlighted by the thiol-X click reaction and activated ester based amidations, considerable efforts have been devoted to developing efficient C-S/C-N bond formation chemistry with these functionalities. [13][14][15][16][17][18][19][20][21][22][23] On the other hand, triggered debonding reactions with high delity to either produce thiol/ amine or use them as an external cue to liberate other molecular identities under mild conditions are very few, though their importance is well recognized.…”

Amphiphilic tri- and tetra-block co-polymers combining versatile functionality with facile assembly into cytocompatible nanoparticles

“…Biodegradable synthetic polymer-drug conjugates have been under active investigation as macromolecular therapeutics for over 40 years, yet there are still relatively few marketed drugs of this type. [1][2][3][4] One major reason for this lack of commercial and clinical translation has been the difficulty in matching the conflicting demands of high therapeutic efficacy with ease of preparation and characterisation. For example, there have been many examples of synthetic polymer-drug conjugates which show high activity in vitro and in pre-clinical in vivo studies.…”

Protein-polymer bioconjugates via a versatile oxygen tolerant photoinduced controlled radical polymerization approach

“…In addition, the unlimited chemical diversity of polymers offers the possibility to convey enhanced properties to natural biomacromolecules. Since the first generation of PEGylated proteins several decades ago [9][10][11][12] , hydrophilic protein-polymer bioconjugates of remarkable complexity and diverse functionality have evolved 8,[13][14][15][16][17][18][19] .…”