Poly amino-acids

In Industrial Chemicals. Recendy, as some amino acids (eg, L-glutamic acid, L-lysine, glycine, DL-alanine, DL-methionine) have become less expensive chemical materials, they have been employed in various appHcation fields. Poly(amino acid)s are attracting attention as biodegradable polymers in connection with environmental protection (236). 

Licjuid Crystals. Ferroelectric Hquid crystals have been appHed to LCD (Uquid crystal display) because of their quick response (239). Ferroelectric Hquid crystals have chiral components in their molecules, some of which are derived from amino acids (240). Concentrated solutions (10—30%) of a-helix poly(amino acid)s show a lyotropic cholesteric Hquid crystalline phase, and poly(glutamic acid ester) films display a thermotropic phase (241). Their practical appHcations have not been deterrnined. 

Swarc,M. The Kinetics and Mechanism of N-carboxy-a-amino-acid Anhydride (NCA) Polymerization to Poly-amino Acids. Vol. 4, pp. 1—65. 

Several alkyl aryl sulfides were electrochemically oxidized into the corresponding chiral sulfoxides using poly(amino acid)-coated electrodes448. Although the levels of enan-tioselection were quite variable, the best result involved t-butyl phenyl sulfoxide which was formed in 93% e.e. on a platinum electrode doubly coated with polypyrrole and poly(L-valine). Cyclodextrin-mediated m-chloroperbenzoic acid oxidation of sulfides proceeds with modest enantioselectivity44b. 

Allcock HR, Shawn R, and Scopelianos AG. Poly [(amino acid ester) phosphazenes] as substrates for the controlled release of small molecules. Biomaterials, 1994, 1, 5563-5569. 

Another limitation is related to the fact that synthetic poly(amino acids) have rather unfavorable material properties. For instance, most synthetic poly (amino acids) derived from a single amino acid are insoluble, high-melting materials that cannot be processed into shaped objects by conventional fabrication techniques. The often undesirable tendency to absorb a significant amount of water when exposed to an aqueous environment is another common property of many poly (amino acids) (7). Finally, high molecular weight poly-(amino acids) are best prepared via N-carboxyanhydrides which are expensive to make. Hence poly(amino acids) are comparatively costly polymers, even if they are derived from inexpensive amino acids (8). 

Unfortunately, the modification of the side chain is not a generally applicable approach. Among the major, naturally occurring amino acids, only L-lysine has a chemically reactive side chain that would be as readily available for chemical modification as the side chain of glutamic or aspartic acid. Since, however, poly (L-lysine) is known to be toxic (10), its derivatives cannot be candidates for generally applicable biomaterials. Thus, most of the poly(amino acids) that have so far been suggested as biomaterials are derivatives of gluteunic or aspartic acid or copolymers of such derivatives with leucine, methionine, or a limited number of additional amino acids (11). 

In view of these constraints, we recently suggested a different strategy for the improvement of the material properties of synthetic poly (amino acids) (12). Our approach is based on the replacement of the peptide bonds in the backbone of synthetic poly(amino acids) by a variety of "nonamide" Linkages. "Backbone modification," as opposed to "side chain modification," represents a fundamentally different approach that has not yet been explored in detail and that can potentially be used to prepare a whole family of structurally new polymers. 

Whereas conventional poly (amino acids) are probably best grouped together with proteins, polysaccharides, and other endogenous polymeric materials, the pseudopoly (amino acids) can no longer be regarded as "natural polymers." Rather, they are synthetic polymers derived from natural metabolites (e.g., a-L-amino acids) as monomers. In this sense, pseudopoly (amino acids) are similar to polylactic acid, which is also a synthetic polymer, derived exclusively from a natural metabolite. 

The use of backbone-modified poly (amino acids) as biomaterials was first suggested by Kohn and Langer (17) who prepared a polyester from N-protected trans-4-hydroxy-L-proline, and a poly(itiuno-carbonate) from tyrosine dipeptide as monomeric starting material (12,18). 

Our interest in the synthesis of poly (amino acids) with modified backbones is based on the hypothesis that the replacement of conventional peptide bonds by nonamide linkages within the poIy(amino acid) backbone can significantly alter the physical, chemical, and biological properties of the resulting polymer. Preliminary results (see below) point to the possibility that the backbone modification of poly(amino acids) circumvents many of the limitations of conventional poly(amino acids) as biomaterials. It seems that backbone-modified poly (amino acids) tend to retain the nontoxicity and good biocompatibility often associated with conventional poly (amino acids)... 

So far only a small number of backbone-modified poly (amino acids) have been prepared and carefully characterized. This chapter therefore represents an account of the initial investigations of this interesting and promising group of polymers. 

Apparently there are no mild chemical reactions that can be used to transform the amide linkages in the backbone of conventional poly-(amino acids) into nonamide linkages such as ester, urethane, or carbonate bonds. Consequently, it is usually not possible to simply replace the backbone amide bonds of conventional poly (amino acids) by nonamide linkages. Pseudopoly(amino acids) must therefore be prepared from scratch by suitably designed polymerization reactions. 

The easy processibility of hydroxyproline-derived polyesters is in marked contrast to the unfavorable material properties of most conventional poly (amino acids) that cannot usually be processed into shaped objects by conventional polymer-processing techniques (7). Furthermore, since the synthesis of poly(N-acylhydroxyproline esters) does not require the expensive N-carboxyanhydrides as monomeric starting materials, poly(N-acylhydroxyproline esters) should be significantly less expensive than derivatives of conventional poly(hy-droxyproline). 

A thoirough and still valid discussion of the basic physiced properties of synthetic poly (amino acids) was written by C. H. Bamford, A. Elliott, and W. E. Hanby, Synthetic Polypeptides. Academic Press, New York, 1956. 

Kohn, J., and Langer, R., Non-peptide poly(amino acids) for biodegradable drug delivery systems, in Proceedings of the 12th International Symposium on Controlled Release of Bioactive Materials (N. A. Peppas and R. J. Haluska, eds.). Controlled Release Society, Lincolnshire, IL, 1985, pp. 51-52. 

Sela, M., Synthetic antigens and recent progi ss in immunology, in Peptides. Polypeptides and Proteins. Proceedings of the Rehovot Symposium on Poly (Amino Acids), Polypeptides and Proteins, John Wiley and sons, New York, 1974, pp. 495-509... 

Uchegbu and coworkers have studied the complexation and delivery of DNA using a unique poly(amino acid)-based polymer vesicle. A polymer of either poly (L-lysine) or poly(L-omithine) was functionalized with methoxy-poly(ethylene glycol) (mPEG) and hydrophobic palmitic acid chains to synthesize an amphiphilic triblock of either mPEG-6-poly(L-lysine)-6-palmitoyl or mPEG-Z>-poly(L-omithine)-6-palmitoyl. Vesicles formed from these polymers were complexed with DNA and showed improved transfection in vitro over poly(amino acid) complexed with DNA or DNA alone [82]. 

Oxidoreductases Transferases Hydrolases Lyases Isomerases Ligases Phenolic polymers, polyanilines, vinyl polymers Polysaccharides, cyclic oligosaccharides, polyesters Polysaccharides, polyesters, polycarbonates, poly(amino acid)s, polyphosphates... 

Enzymes are generally classified into six groups. Table 1 shows typical polymers produced with catalysis by respective enzymes. The target macromolecules for the enzymatic polymerization have been polysaccharides, poly(amino acid)s, polyesters, polycarbonates, phenolic polymers, poly(aniline)s, vinyl polymers, etc. In the standpoint of potential industrial applications, this chapter deals with recent topics on enzymatic synthesis of polyesters and phenolic polymers by using enzymes as catalyst. 

A polynucleoside with an unnatural polymeric backbone was synthesized by SBP-catalyzed oxidative polymerization of thymidine 5 -p-hydroxyphenylacetate. Chemoenzymafic synthesis of a new class of poly(amino acid), poly(tyrosine) containing no peptide bonds, was achieved by the peroxidase-catalyzed oxidative polymerization of tyrosine ethyl esters, followed by alkaline hydrolysis. Amphiphile higher alkyl ester derivatives were also polymerized in... 

J. R. Bruton and H. C. McLaurine. Modified poly-amino acid hydration suppressant proves successful in controlling reactive shales. In Proceedings Volume, pages 127-135. 68th Annu SPE Tech Conf (Houston, TX, 10/3-10/6), 1993. 

Polyanhydrides Polyorthoesters Poly(amino acids) Psuedopolyamino acids Polyphosphazenes... 

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