Peptide-Functionalized Polymers

Amino acid and amino ester bearing polymers are useful models of the naturally occurring proteins and peptides, in which the nature and sequence of the monomer units determine the biological activity of the resulting polymer [20]. Thus, by choosing suitable monomers, simple mimics of biopolymers could be obtained. Moreover, since the amino acid and amino ester moieties are hydrolytically unstable, many drugs can be linked to the polymer scaffold by this type of linkages [10]. 

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Figure 7.3 Peptide-functionalized polymers, (a) Poly(NBE-graft-(y-benzyl-L-glutamate), (b) block copolymer of protein tropoelastin PONBE with PEG-functionalized PONBE, and (c) poiy(cyclobutene carboxamide).

Urry, D. W. (1998). Five axioms for the functional design of peptide-based polymers as molecular machines and materials Principles for macromolecular assemblies. Peptide Sri. 47, 167-178. 

The equilibrium of the ADMET polymerization is forced towards high polymer by running bulk polymerizations under vacuum to remove ethylene. Working under bulk conditions or in solution, ADMET polymer products have been isolated up to 80 kg mol using [Mo] on hydrocarbon monomers and up to 70 kg mol" using [Ru]" on peptide functionalized monomers [39,40]. 

Peptide-based polymers 62, containing imidazole, carboxyl, and hydroxymethyl functionalities, have been prepared from optically active 50d and tested as mimics of enzymes, such as chymotrypsin, which have the same functionalities (Scheme 41) [70]. These polymers exhibit markedly higher activities than the corresponding low molecular weight compounds in the hydrolysis of nitrophenyl and dinitrophenyl esters. Increased activities were... 

Synthetic peptide-based polymers are not new materials homopolymers of polypeptides have been available for many decades and have only seen hmited use as structural materials [5,6]. However, new methods in chemical synthesis have made possible the preparation of increasingly complex polypeptide sequences of controlled molecular weight that display properties far superior to ill-defined homopolypeptides [7]. Furthermore, hybrid copolymers, that combine polypeptide and conventional synthetic polymers, have been prepared and combine the functionality and structure of peptides with the processabihty and economy of polymers [8,9]. These polymers are well suited for applications where polymer assembly and functional domains need to be at length scales ranging from nanometers to microns. These block copolymers are homogeneous on a macroscopic scale, but dissimilarity between the block segments typically results in microphase heterogeneity yield-... 

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]. 

Merrifield resin was reacted with tetrachlorohydroquinone to give a polymeric monobenzyl ether of tetrachlorohydroquinone (77) (0.7mmolg 1 loading). The esters of this functionalized polymer act as polymeric active esters, which have been used for the acylation of amines and the synthesis of some peptides when using the corresponding active esters of N-protected amino acids [95],... 

FIGURE 2.7 An alternative functional polymer. Proteins are built of amino acids linked by peptide bonds. 

A.D. Aguilar, E.S. Forzani, X.L. Li, N.J. Tao, L.A. Nagahara, I. Amlani, and R. Tsui, Chemical sensors using peptide-functionalized conducting polymer nanojunction arrays, Appl. Phys. Lett., 87, 193108 (2005). 

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