Protein–polymer therapeutics: a macromolecular perspective

Abstract

The development of protein-polymer hybrids emerged several decades ago with the vision that their synergistic combination will offer macromolecular hybrids with manifold features to succeed as the next generation therapeutics. From the first generation of protein-polymer therapeutics represented by PEGylated proteins, the field has since advanced, reinforced by the progress in contemporary chemical techniques for designing polymeric scaffolds and protein engineering. Novel polymerization techniques that offer multifunctional strategies as well as a greater understanding of proteins and their biological behavior have both proven to be exceptional tools in the construction of these hybrid materials. In this review, we seek to summarize and highlight the recent progress in these semi-synthetic protein hybrids in terms of their preparation, design, resulting bioarchitectures and bioactivities for their intended bio-applications.

Spin‐labeling of polymeric micelles and application in probing micelle swelling using EPR spectroscopy

“…The disulfide bond of our spin labels can be cleaved with a reducing reagent; the resultant active thiols can facilitate inter‐polymer cross‐linking or be used to attach a different label or chemical “tag.” The mild reaction conditions also help when using our approach to investigate biological‐relevant problems. For example, being able to spin label polymers in aqueous phase will allow us to probe the structural information of protein‐polymer or peptide‐polymer hybrid materials . Of course, the disulfide bond has less stability and caution must be taken when operating the R1 labeled polymers.…”

Engineering protein nanocages as carriers for biomedical applications

“…1 PEG acts as a stealth layer shielding the immunogenic epitopes on the surface of the nanocage structure. 73 This layer prevents the protein opsonin from adsorbing onto the surface, thereby shunting the recognition of the nanocage by phagocytic cells (reticuloendothelial system). 42 The PEG modification also benefits the tuneable solubility and structural integrity of the protein nanocage.…”

“…42 The PEG modification also benefits the tuneable solubility and structural integrity of the protein nanocage. 73 The spatial control of multifunctional groups on protein nanocages equips them for both hierarchical self-assembly and display of distinct functional ligands. Display of multiple types of ligands in a precise arrangement on nanoparticles is challenging.…”

Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

“…Proteins play a significant role in biological functions and are one of the most versatile building blocks in biology due to their diverse structural and functional properties . Due to their unique bioactivities and high biocompatibility, the therapeutic usage of proteins is emerging . However, protein therapeutics also have some inherent drawbacks such as poor stability, sometimes high immunogenicity and antigenicity or low blood circulation times .…”

“…2016, 22, 17112 -17129 www.chemeurj.org their unique bioactivities and high biocompatibility, the therapeutic usage of proteins is emerging. [99,100] However, protein therapeutics also have some inherent drawbacks such as poor stability, sometimes high immunogenicity and antigenicity or low blood circulation times. [101,102] PEGylation of proteins represents a common strategy where the polymers are adopted as high-molecular-weight substituents to enhance pharmacokinetic parameters and promote accumulation of the proteins in tumour tissue.…”