Peptide-containing monomers

In this review the different synthetic strategies for constructing polymer-peptide hybrids will be discussed, as well as some of the characteristic features of the materials. The complexity of the hybrid structures prepared will increase as this review progresses, starting with the controlled polymerization of peptide-containing monomers and later covering the creation of block copolymer structures via a protein engineering approach. 

Peptidomimetics in which one amide bond is replaced by a phosphinic acid (R-P(0H)(=0)-R phosphinic peptides ) are of interest as potential protease inhibitors [17-19]. These compounds have been prepared either from orthogonally protected phosphorus-containing monomers [17,18,20], or by forming the phosphorus-containing fragments on solid phase, as sketched in Figure 11.4 [19,21], Phosphinic acids have been prepared on solid phase mainly by reaction of carbon electrophiles with monoalkylphosphinates. As carbon electrophiles, acrylates, aldehydes, reactive alkyl halides, or a, 3-unsaturated ketones can be used. 

There are in general two ways to synthesize side chain polymers, polymerization of peptide-functional monomers or introduction of the peptide moiety afterwards, by grafting. The latter technique is based on the synthesis of polymers containing some form of functionality in the side chain, normally an activated ester moiety, which can further react with a peptide. The most commonly used method for the polymerization of monomers containing active esters is free radical polymerization. In particular many activated acrylate esters have been polymerized in this manner [12] (Table 1) for use in a wide variety of applications, from the preparation of polymer drug conjugates [13,14] to supports for solid phase peptide synthesis [15,16]. 

The major drawback to using the grafting approach is that it is very difficult to achieve and/or determine 100% functionalization of the polymer side chains. To overcome this problem, another approach has been developed, in which the monomer already contains the peptide fragment of interest. Therefore, after polymerization, every monomer unit is inherently functionalized [21]. The disadvantage of this method is that synthesizing peptide-based monomers is not trivial, and compatibility issues between polymerization method and peptide moiety have to be taken into account. 

A number of researchers have explored chemical s)mthesis of adhesive protein polypeptide and polymer analog. The synthetic approaches typically involve polymerization of catechol or DOPA-containing monomers, as well as post-polymerization derivatization of polymer endgroups or side chains with DOPA, DOPA peptides or DOPA mimetic molecules. A sampling of chemical stmctures is provided in Schemes 2-4 and described below. 

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