Polymers conjugation strategy

Gauthier MA, Klok HA (2008) Peptide/protein-polymer conjugates synthetic strategies and design concepts. Chem Commun 23 2591-2611... 

Bontempo and Maynard first reported CRP directly from a protein. This technique, known as grafting from, involves the use of a protein macroinitiator for ATRP or macroCTA for RAFT polymerization. This strategy has several advantages. Purification is easier because only small molecules rather than polymer chains need to be removed. In addition, characterization can be simpler because the site of polymer attachment is predetermined by the attachment of the initiator or CTA fragment, which is easier to analyze. Finally, hydrophobic polymer conjugates are more readily prepared.However, some desired monomers are insoluble in the aqueous systems... 

Beyond these three main concepts, the inverse bioconjugation approach offers another strategy to connect peptides or proteins with synthetic polymers. Using a solid support, which is preloaded with a polymer block, the biological molecule can be assembled in a stepwise fashion through solid-phase synthesis. Mutter and coworkers first showed the attachment of PEO to a poly(styrene) resin via a benzyl ether linker. This concept was finally developed further by Bayer and Rapp leading to a commercially available PAP resin, which is widely applied in solid-phase peptide synthesis. In a similar approach. Lutz, Borner, and coworkers demonstrated the preparation of cleavable and non-cleavable soluble polystyrene supports by ATRP for the liquid-phase synthesis of peptide-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... 

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