Protein-polymer bioconjugates

Johnson RP, John JV, Kim 1 (2013) Recent developments in polymer-block-polypeptide and protein-polymer bioconjugate hybrid materials. Eur Polym J 49(10) 2925-2948. doi 10.1016/j. eurpolymj. 2013.04.017... 

Highly boron doped diamond BDD Protein-polymer bioconjugate [216]... 

Fluorescently Labeled Protein-Polymer Bioconjugates Using Protein-Derived Macroinitiators from Living Radical Polymerization... 

Trubetskoy, V.S., Narula, J., Khaw, B.A., and Torchilin, V.P. (1993) Chemically optimized antimyosin Fab conjugates with chelating polymers Importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization. Bioconjugate Chem. 4, 251-255. 

Woghiren C, Sharma B, Stein S (1993). Protected thiol-polyethylene glycol a new activated polymer for reversible protein modification. Bioconjug. Chem. 4 314-318. 

Won, J. L, Meagher, R. J., and Barron, A. E. Characterization of glutamine deamidation in a long, repetitive protein polymer via bioconjugate capillary electrophoresis. Biomacwmolecules 5, 618-627 (2004). 

Over the last decades, several academic and industrial research programs have been focused on the development and production of appropriate biocompatible formulations that provide enhanced therapeutic performance. Three different strategies can be discerned that are applied separately or in combination (i) addition of excipients to proteins, such as protease inhibitors, penetration or absorption enhancers like bile salts, fatty acids, cyclodextrins or surfactants " (ii) modification of the physicochemical properties of proteins, e.g. by attachment of lipophilic or hydrophilic moieties or (iii) incorporation of proteins into polymeric or liposomal delivery carriers. " A variety of polymeric vectors has been developed and exploited for this purpose, including biodegradable nanoparticles, nanogels, micelles, polymer bioconjugates and soluble nanocomposites. These polymeric carriers are more extensively described in the following sub-sections. 

ATRP is an exceptional tool for the synthesis of polymer-bioconjugates via grafting from technique from biomolecules such as proteins and peptides and even from high-value small molecule dmg entities. These molecules can be convenientiy modified to form suitable ATRP initiators to produce polymer-bioconjugates. Representative examples for polymer-bioconjugates prepared by ATRP using various functional biological initiators are illustrated in Fig. 2.23 [78]. 

Unfortunately, utilization of copper(i) to control the regioselectivity yields several problems. Although only catalytic amounts are required, copper can induce cytotoxic effects and protein denaturation, ° which can complicate bioconjugation by CuAAC for applications in vitro and in vivo. In addition, copper salts are often rather difficult to remove from the reaction products. Nevertheless, advantages like high selectivity, mild reaction conditions, and almost quantitative product formation have proven CuAAC highly beneficial for the preparation of site-specific peptide- and protein-polymer conjugates. 

Besides the chemoenzymatic approaches described above, where functional groups are added to allow for conjugation with other macromolecules, enzymes demonstrate other possibilities to obtain peptide- and protein-polymer conjugates, which are normally difficult to obtain by common chemical synthetic strategies. Enzyme responsiveness can be used to modulate bioconjugate properties in order to create hybrid materials with... 

Narain, R. (2006) Tailor-made protein-glycopolymer bioconjugates, Reactive Functional Polym., 66, 1589-95. 

Shimoboji, T., Ding, Z. L., Stayton, P. S. and Hoffinan, A. S. (2001) Mechanistic Investigation of Smart Polymer-Protein Conjugates, Bioconjugate Chem., 12, 314—9. 

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