Tyrosine-derived polyarylates

Figure 2 Synthesis of tyrosine-derived polyarylates. DIPC, 1,3-diisopropylcarbodiimide DMAP, dimethylaminopyridine PTSA, p-toluenesulfonic acid.

Tyrosine-derived polyarylates (Fig. 1.23) these materials are obtained starting from the tyrosine-derived monomers described above and alkyl... 

Figure 4 Reaction scheme for ihe preparation of tyrosine-derived polyarylates. This reaction scheme is a copolymerization of a diphenol component and a diacid component. The diphenol components are the same desaminotyrosyl-tyrosine alkyl esters used in the synthesis of polycarbonates (Fiipire 3). The pendent chain Y is ethyl, butyl, hexyl, or octyl. The diatid components are succinic acid, adipic acid, suberic acid, and sebacic acid providing a flexible backbone spacer (R) having 2, 4, 6, and 8 methylene groups respectively. DIPC = diisopropylcarbodiimide.

Table 2 Some Physical Properties of Selected Tyrosine-Derived Polyarylates ... 

Figure 6a Glass transition temperatures of tyrosine-derived polyarylates. In this three dimensional presentation, the pendent chain length is plotted on the y axis, the length of the diacid component in the polymer backbone is plotted on the x axis, and the measured glass transition temperatures are plotted on the z axis.

In a series of preliminary puhlications, the cellular response to tyrosine-derived polyarylates was explored using chick embiyo dorsal root ganglia cells (Kohn, 1994) and rat lung fibroblasts (Zhou, 1994), wth no indications of cytotoxicity. Preliminary data indicate that the ability of cells to attach and grow on polyarylate surfaces was strongly correlated with the surface hydrophobicity of the polymers (as measured by the air-water contact angle). 

Tyrosine-derived polyarylates offer the ability to alter wdely the polymeric properties by changes in either the backbone or the pendent chain structure. These polymers appear most adept at addressing medical implant needs where a slowly degrading, relatively flexible and soft polymer is required. 

S.L. Bourke, J. Kohn, Polymers derived from the amino acid 1-tyrosine polycarbonates, polyarylates and copolymers with poly(ethylene glycol), Adv. Drug Deliv. Rev. 55 (2003) 447-466. 

Pseudo-poly(amino acids) were first described in 1984 (Kohn, 1984) and have since been evaluated for use in several medical applications (Kohn, 1987 Yu-Kwon, 1989 Zhou, 1990 Kohn, 1993 Mao, 1993). Although a range of different pseudo-poly(amino acids) has been prepared, detailed studies of the physical properties, biological properties, and possible applications of these polymers have so far been conducted only for a select group of new tyrosine- derived polycarbonates, polyiminocarbonates, and polyarylates. This review will encompass the work to date on these specific materials. 

In dew of the nonprocessibility of conventional poly(L-tyrosine), which cannot be used as an engineering plastic, variational derivatives were emlsioned. The development of tyuosine-based polycarbonates, polyarylates and polyiminocarbonates represents the first time tyrosine-derived polymers wth favorable engineering properties have been identified. 

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