Glutamic acid-tyrosine copolymers

Figure 7a. Effect of tyrosine residues in copolymers with glutamic acid on the yields...

Copolymer is prepared by copolymerization of the N-carboxyanhydrides of tyrosine, alanine, lysine, and glutamic acid. The polymerisation was carried out at ambient temperature in anhydrous dioxane with diethylamine as initiator. Glatiramer Acetate have the ratio alanin glutamic acid lysine tyrosine = 1 6 4.54 2. 

Some other peptides, e.g., dipeptidyl peptidase IV (8), endopeptidase 3.4.24.16 inhibitor (9), and a copolymer of tyrosine, glutamic acid, alanine, and lysine (10), have also demonstrated immunomodulatory activity. Thus analogues of these may some day play an important role in treatment of autoimmune and inflammatory diseases. It should also be noted that a vast number of naturally derived peptides also has demonstrated antimicrobial activity toward a wide range of pathogens (11), resulting in possible templates for further optimization studies clearly demonstrating the potential importance of peptides as pharmacological tools. 

Earlier studies include those of Merrifield and Wooley (i27) and of Katchalski et al. (128). They prepared poly-L-histidine and its copolymers with other amino acids and showed them to be active in the hydrolysis of PNPA. Noguchi and Saito prepared poly-L-histidine, its copolymers with other amino acid residue (glutamic acid 2, aspartic acid 3, serine 4, alanine 5, cystein 6, lysine 7, e-aminocaproic acid S, and tyrosine 9), and various dipeptides containing the histidyl residue 1), (129,130). The... 

Fig. 8. Moffitt plots at two different values of Xo, 212 and 216 m, for the dispersions of a copolymer of 6% i.-tyrosine with n-glutamic acid (PTGA) from 700 m i down to 240 m/i.. The plots based upon 212 m/i are an extension of the visible and near ultraviolet data represented in detail in Fig. 7. Helical form in 0.1 M phosphate buffer,...

I960), but in another solvent, ethylene dichloride, a Xo value of 208 ma was required to make the plot linear down to 248 m/i (Savitz and Doty, 1958). The dispersion for a helical copolymer of 5% L-tyrosine with L-glutamic acid in 0.1 M phosphate buffer at pH 4.0, the visible and near ultraviolet portion of which is represented in Fig. 7, requires a Xo of 216 mju to bring the data between 240 and 280 mu into line with measurements at higher wavelengths (Fig. 8), As Xo is altered from 212 to 216 mu, bo derived from visible and near ultraviolet data for this polymer changes from —615 to —535. An alteration to 218 m/x is required to correct for a similar nega-... 

Fig. 9. Ultraviolet rotatory dispersions of sperm whale myoglobin and a copolymer of 5% n-tyrosine with L-glutamic acid (PTGA). Myoglobin in 0.1 M phosphate...

Pinna nobilis tropomyosin contains no proline (Bailey, 1957), which is consistent with a helical molecule. As might be expected from the study of a 5% copolymer of L-tyrosine with L-glutamic acid (see Section III, F), the presence of small amounts of tyrosine and histidine in this protein has no appreciable rotatory effect. This protein contains relatively large amounts of amino acids that do form standard helical polypeptides—glutamic acid, 21 % lysine, 8% alanine, 12% and leucine, 12.5 %—but it also has 4 % valine, 6 % serine, and 13 % aspartic acid. If these residues behaved as they and their analogues appear to do in synthetic polypeptides, either pre-... 

Fig. 1. A multichain copolymer in which L-tyrosine and L-glutamic acid residues are attached to multi-poly(DL-alanyl)-poly(L-lysine). Left Tyrosine and glutamic acid located in terminal positions. Right Tyrosine and glutamic acid positioned internally. Horizontal lines, poly(L-lysine) hatched area, poly(DL-alanine) , L-tyrosine O, L-glutamic acid. From M. Sela. ...

Fig. 2.5. Structure of a multichain polymer containing a backbone of polylysine and an external random copolymer of tyrosine and glutamic acid (molar ratio, Lys Tyr Glu D,L-Ala= 1 1.8 3.7 24). The average molecular weight of the polymer used as antigen in the experiments discussed in the text is 35,000. From Fuchs and Sela (27,28).

In one set of experiments (27) a copolymer with the general structure shown in Fig. 2.5 was used to immunize rabbits. Antiserum was eventually obtained which precipitated the immunogen specifically. Precipitation could be inhibited by the random copolymer poly(Tyr,Glu). Maximum inhibition was obtained when the ratio of tyrosine to glutamic acid in the copolymer was 1.0 1.1. When the ratio in the copolymer was 1 4, only partial inhibition was possible, even with very high concentrations of the inhibitor, and no inhibition of precipitation was obtained when the ratio was 1 9 [a ratio widely different from that in the immunogen (Fig. 2.5, legend)]. 

Copaxone [17] Copolymer of L-tyrosine, L-lysine, L-alanine, L-glutamic acid Multiple sclerosis 1996... 

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