Polymer–protein conjugates: an enzymatic activity perspective

Abstract

Proteins have been modified with polymers in diverse manners over the past 30 years. However, while proteins have been used to prepare many functional constructs, they are sensitive biomolecules and their bioactivity can be either positively or negatively influenced by many different aspects of polymer modification. The primary focus of this review article is to highlight the opportunities offered by new trends in protein modification, and specifically how they influence the overall biological activity of the conjugate, including its dependence on temperature and pH. We survey the effect of polymer molecular weight, number of conjugated polymer chains, polymer coupling strategy (including random versus site-specific coupling, ''grafting from'', and multi-point covalent attachment), polymer architecture (including branched and comb-type), polymer interactions with the protein (including electrostatic and host-guest interactions), polymer interactions with enzyme substrate, and polymer biodegradability. We have selected six enzymes, which have been extensively modified with polymers in diverse fashions in the literature, as basis for this discussion. These proteins are L-asparaginase, alpha-chymotrypsin, trypsin, lysozyme, bovine serum albumin, and papain. This review includes polymers such as poly(ethylene glycol) (PEG), polysaccharides, polypeptides, and other synthetic (vinyl) polymers. From the discussed literature we attempt to extract tentative general trends observed between state-of-the-art methods of preparing protein-polymer conjugates and the activity of the conjugate.

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

“…Severe adverse effects and high costs (66) may disqualify TNFα blockers for non-refractory CD, as a GFD is a relatively safe and inexpensive alternative (8). Moreover, periodic administration of biological drugs by trained personnel is expensive and might be addressed by subcutaneous self-injection devices or by developing compounds with long circulation times (e.g., PEGylation technologies) (67).…”

Polymer Directed Protein Assemblies

“…Additionally, many systems are based on combining the protein and the polymer covalently [7]. Covalently connecting the polymer and protein alters the behavior, response and stability of the protein and increases compatibility with other polymeric systems, e.g., in phase-separated block-copolymer system [8,9].…”

RAFT polymerization mediated bioconjugation strategies

“…Readers are also referred to several excellent reviews covering comprehensively the use of living radical polymerizations in bioconjugations. [13][14][15][16]25 Within this review, the term ''biomolecule'' has been used to refer to the molecules originating from a living organism and the synthetic analogs of such molecules. Thus, the conjugates of synthetic peptides and nucleic acids have been included in the review.…”

“…42,43,[44][45][46][47][48][49][50][51] RAFT polymerization offers a highly versatile platform for controlled synthesis and molecular engineering of polymer bioconjugates. [13][14][15][16]25 The strength of the RAFT approach for generation of polymer bioconjugates lies in its ability to control the polymerization of a wide range of monomers in varying solvents including water, at moderate temperatures, using only chain transfer agents and common free radical initiators (without the need for any additional polymerization component such as metal catalysts and sacrificial initiators). Moreover, it enables the synthesis of well-defined polymers with defined and spatiallycontrolled chemical functionalities such as pendant-, mid-junction, alpha-and omega-end-group functionalities, suitable for performing bioconjugations.…”