Cystine synthesis

Growing chicken128 and hens129 utilize sulphate sulphur for cystine synthesis. Biological radio-tracer experiments130 with Na235S04 (10 fiCi) have shown that over 65% of the 35S administered to a 24-hour-old embryo is incorporated into taurine of the chick. No radioactive cystine, methionine or cysteic acid was detected in the hydrolysate obtained from the embryo and only a small portion of total taurine-35S occurs as taurocholic acid. The embryo is unable to utilize sulphate sulphur for cystine synthesis. 

Cysteine [52-90 ] is a thiol-bearing amino acid which is readily isolated from the hydrolysis of protein. There ate only small amounts of cysteine and its disulfide, cystine, in living tissue (7). Glutathione [70-18-8] contains a mercaptomethyl group, HSCH2, and is a commonly found tripeptide in plants and animals. Coenzyme A [85-61-0] is another naturally occurring thiol that plays a central role in the synthesis and degradation of fatty acids. 

The synthesis commences with a straightforward acylation of the primary amino group of L-cystine dimethyl ester (13) with 5-hexy-noyl chloride (14) to give amide 12 in 90% yield (see Scheme 3). The action of zinc dust in acetic acid on intermediate 12 accom-... 

A newer therapeutic approach is the administration of betaine (6-12 g daily), which lowers homocysteine levels by favoring remethylation [33], A theoretical hazard of betaine treatment is increasing the blood methionine, sometimes to an extravagant degree ( 1 mmol/1). Experience to date indicates that betaine administration is safe, with no major side effects except for a fishy odor to the urine. Other therapeutic approaches have included the administration of salicylate to ameliorate the thromboembolic diathesis. Patients also have been treated with dietary supplements of L-cystine, since the block of the transsulfura-tion pathway in theory could diminish the synthesis of this amino acid. 

Sanchez-Cano et al. have proposed paired synthesis for obtaining L-cysteic acid and L-cysteine from L-cystine which greatly improves the economical parameters [57], The global process-flow for the paired synthesis, with L-cystine and water as starting materials is shown in Fig. 3. Table 2 compares the results for the paired (B) and the individual syntheses (A, C). 

THE SULFHYDRYL GROUP OF CYSTEINE AND THE SYNTHESIS OF PEPTIDES CONTAINING CYSTINE... 

FIGURE 6.20 Synthesis of cystine-containing peptides from cysteine-containing peptides by removal of other protectors followed by (A) deprotection of the sulfhydryls and their oxidation to the disulfide, and (B) formation of the disulfide bond by reaction of a liberated sulfhydryl with a sulfhydryl that is protected and activated by 3-nitro-2-pyridylsulfanyl (Npys).89... 

The synthesis of peptides containing cystine is rarely performed starting with derivatives of cystine because of the obstacle of disulfide interchange. Disulfide interchange was discovered by F. Sanger during his attempts to determine the primary... 

FIGURE 6.22 Disulfide interchange.92 (A) Discovered in synthesis when hydrazinolysis of an unsymmetrical derivative of cystine gave two symmetrical products instead of the expected monohydrazide at the urethane-protected cysteine moiety of the derivative.95 (B) Mechanism for interchange catalyzed by strong acid,94 which is suppressed by thiols. (C) Mechanism for interchange catalyzed by weak alkali, which is enhanced by thiols. 

FIGURE 6.23 The synthesis of insulin, starting with a cystine-containing peptide. [Kamber et al., 1977]. Moc = methoxycarbonyl, Bpoc = biphenylisopropoxycarbonyl, Trt = trityl, Acm = acetamidomethyl. (a) HOBt-assisted carbodiimide-mediated coupling (b) removal of Trt by HC1 in CF3CH2OH-CH2Cl2 (9 1) at pH 3.5 (c) removal of Bpoc by CF3CH2OH-CH2 Cl2 (9 1) at 60°C (d) removal of Acm and oxidation by iodine. 

Hu Z, Guan WC, Tang XY, Huang LZ, Xu H (2007) Synthesis of water-soluble cystine C derivative with catalyst and its active oxygen radical scavenging ability. Chin. Chem. Lett. 18 51-54. 

The synthesis of cystine by Erlenmeyer jun. in 1903, which was more fully described by him and Storp in 1904, showed that Friedmann s formula was correct —... 

Another synthesis of cystine was described by Fischer and Raske in 1908 (see page 75) which is similar to that of Erlenmeyer. 

Fischer and Suzuki soon afterwards showed that Neuberg and Mayer s stone cystine contained tyrosine, and that its different behaviour to protein cystine was due to the presence of this compound. Rothera also could find no difference between stone cystine and protein cystine, and further, Gabriel s synthesis of isocysteine or a-thio-/8-aminopropionic acid and isocystine, which had quite different properties to cystine, though the two were much alike in many of their reactions, proved that stone cystine and protein cystine must be identical substances. Finally, it has been shown by Friedmann that a-thiolactic acid, ammonia PT. I. 4... 

Thus, the work of Friedmann on the constitution of cystine, its synthesis by Erlenmeyer jun. and by Fischer, definitely show that it has the composition... 

Kamber B, Hartmann A, Eisler K, Riniker B, Rink H, Sieber P, Rittel W. The synthesis of cystine peptides by iodine oxidation of 5-trityl-cysteine and S-acetamidomethyl-cysteine peptides. Helv Chim Acta 1980 63 899-915. 

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