Poly-L-tyrosine

The first member of this series, poly(CTTE), was a high-melting and virtually insoluble polymer that could not be processed into shaped objects by any one of the conventional polymer-processing techniques. In this respect, poly(CTTE) was highly reminiscent of conventional poly(L-tyrosine). 

This series of polymers made it possible to investigate the contribution of each type of pendant chain separately. Poly(Dat-rym), the polymer carrying no pendant chains at all, was virtually insoluble in all common organic solvents. Due to its thermal instability in the molten state, poly(Dat-Tym) could be neither compression-nor injection-molded. In this respect, the processibiUty of poly(Dat-Tym) was not improved as compared to conventional poly(L-tyrosine). 

In order to test the tissue compatibility of tyrosine-derived poly-(iminocarbonates), solvent cast films of poIy(CTTH) were subcutaneously implanted into the back of outbread mice. In this study, conventional poly(L-tyrosine) served as a control (42). With only small variations, the experimental protocol described for the biocompatibility testing of poly(N-palmitoylhydroxyproline ester) (Sec. III. 

Since poly(L-tyrosine) cannot be processed into shaped devices, compressed pellets rather than solvent cast films were used as control implants. Poly(L-tyrosine) formed strikingly yellow, moderately inflamed patches that remained at the implantation site throughout the 1-year study. Contrary to soluble proteins or peptides that ar rapidly degraded by enzymes, implants of conventional poly(L-tyro-sine) were evidently nondegradable over a 1-year period. At wee 56 all poly(L-tyrosine) implants were infiltrated by a moderate n ber of inflammatory cells. 

Applequist and Mahr (114) proposed the use of Buckingham s equation (see the next subsection) for ellipsoids of revolution to calculate vacuum of rodlike molecules. They found for poly-L-tyrosine in quinoline that the values of 1/2 so computed from experiment varied linearly with molecular weight and yielded (4.94 0.014) D for fa. In this case, the molecular weights of the samples were indirectly estimated from the observed rotational relaxation times with the assumption of the relation for rigid rods. 

If the side chains have strongly chromophoric groups near the backbone, such as in polymers of aromatic amino acids like poly(L-phenylalanine), poly(L-tyrosine), and poly(L-tryptophan), the CD spectrum is strongly dependent on the side chains and is totally different from the standard spectra of polypeptides lacking chromophoric groups in the side chains. This is due to the interactions between amide and aro-... 

Fig. 30. Energy contours (involving all possible interactions of the side chains) for the right-handed a-helix (0=132° and 0=123°) of poly-L-tyrosine, with Z> = 4, in kcal mole-l/residue. The position of lowest energy is indicated by the small cross near yi = 300, 150 (Ooi et al., 1967).

L14. Lehrer, S. S., and Fasman, G. D., Ultraviolet irradiation effects in poly-L-tyrosine and model compounds. Identification of bityrosine as a photoproduct. Biochemistry 6, 757-767 (1967). 

T. Ooi, R. A. Scott, G. Vanderkooi, and H. A. Scheraga, / Chem. Phys., 46, 4410 (1967). Conformational Analysis of Macromolecules. IV. Helical Structures of Poly-L-atanine, Poly-L-valine, Poly-B-methyl-L-aspartate, Poly y-methyl-L-glutamate, and Poly-L-tyrosine. 

Of polypeptides with unusual chromophoric attributes, poly-L-tyrosine is the most thoroughly studied. X-ray and infrared evidence demonstrate that this polypeptide is a-helical in films cast from dimethyl formamide (Downie et al., 1959), and hydrodynamic studies have established that it exists as a helix in solution as well (Coombes et al., 1960). The helical form, which is stable in both dimethyl formamide and aqueous solution of pH 10.85, may be transformed into the random coil either by increasing the... 

Gruchalla RS, Sullivan TJ. Detection of human IgE to sulfamethoxazole by skin testing with sulfamethoxazoyl-poly-L-tyrosine. J Allergy Clin Immunol 1991 88(5) 784-92. 

The shapes of the absorption, fluorescence and phosphorescence spectra of the homopolymers are basically unchanged from those of the monomers and for the most part only minor shifts are noted in the wavelengths. The molar extinction coefficients of the polymers indicate a ochromic effect in poly-L-tr3q)tophan and poly-L-tyrosine 120) but a Ay e chromic effect in poly-L-phenylalanine 121). 

Fig. 11. Total emission and phosphorescence spectra of aromatic polyamino acids in diglyme solvent at 77 °K. Amino acid concentration is 5 x 10 M. Total emission spectra (A) poly-L-phenylalanine (10 mv) (B) poly-L-tyrosine (100 mv) (C) poly-L-tryptophan(200mv).Phosphorescence spectra (D) poly-t-phenylalanine (1 mv) (E) poly-L-tr3 tophan (1 mv) (F) poIy-L-tyrosine (10 mv). The amplifier gain setting is given in parentheses. (From Longworth n )).

The quantum sddds of phosphorescence of the homopolymers are drastically reduced relative to the monomers. Since the phosphorescence lifetimes and fluorescence yields are not as severely affected in poly-L-tryptophan and poly-L-tyrosine, incorporation into the regular poly-... 

Dimers of t3n osine are readily formed as a photoproduct upon irradiation of poly-L-tyrosine Possibly the mechanism involves the initial formation of the t5o osine triplet state with subsequent photoejection of an electron, and the loss of a proton to form a neutral phenoxyl radical which attacks a neighboring t5n osine to form the 0—O -dihy-droxy diphenyl compound 28b),... 

A synthetic immunogen, poly-(L-tyrosine-L-glutamic acid)-poly-DL-alanine-poly-L-lysine has been used to raise immunoglobulin M in rabbits and cattle. The immobilized antigen has then been used in the purification of the immunoglobulin. 

Poly-L-tyrosine absorbs strongly at 1515cm . A band at this frequency has been found in a number of proteins (e.g., a-keratin, ribonuclease, and insulin) and was considered to be due to the tyrosine residue (Bendit, 1967). This assignment was confirmed by examination of the spectra of deuterated proteins which usually exhibit this band at 1513 cm . ... 

Fig. 10.16. Comparison of the ratio Dt /D, for poly-L-tyrosine cast from dimethylformamide with the extrapolated straight line determined for the proteins in Fig. 10.15. (Bendit, 1967.)...

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