S-Phenyl-L-cysteine

Background: S-Phenyl-L-cysteine is regarded as having potential applicability as an antiretroviral/protease inhibitor for human immunodeficiency virus (HIV). In the present study, optically active S-phenyl-L-cysteine was prepared in a highly efficient manner from inexpensive bromobenzene using tryptophan synthase through a chemoenzymatic method. Results: The chemoenzymatic method used a four-step reaction sequence. The process started with the reaction of magnesium and bromobenzene, followed by a Grignard reaction, and then hydrolysis and enzymatic synthesis using tryptophan synthase. Through this approach, S-phenyl-L-cysteine was chemoenzymatically synthesized using tryptophan synthase from thiophenol and L-serine as the starting material. Conclusions: High-purity, optically active S-phenyl-L-cysteine was efficiently and inexpensively obtained in a total yield of 81.3% (> 99.9% purity).

An economical method for production of S-phenyl-L-cysteine from keratin acid hydrolysis wastewater (KHW) containing L-serine was developed by recombinant tryptophan synthase. This study provides us with an alternative KHW utilization strategy to synthesize S-phenyl-L-cysteine. Tryptophan synthase could efficiently convert L-serine contained in KHW to S-phenyl-L-cysteine at pH 9.0, 40°C and Trion X-100 of 0.02%. In a scale up study, L-serine conversion rate reach 97.1% with a final S-phenyl-L-cysteine concentration of 38.6 g l(-1).

Tellurium compounds are effective antioxidants and chemoprotectors, even more active than their selenium and sulfur analogues. In addition to these properties, some selenium compounds, such as selenocysteine Se-conjugates, possess significant chemopreventive and antitumor activities, and selenol metabolites are considered as active species. In the present study, we have synthesized Te-phenyl-L-tellurocysteine and evaluated its bioactivation and cytotoxicity. The activities of this compound were compared with those of the corresponding selenium and sulfur analogues. Te-Phenyl-L-tellurocysteine is bioactivated into its corresponding tellurol, as detected by GC-MS, by cysteine conjugate beta-lyase and amino acid oxidase, analogously to what has been shown previously for Se-phenyl-L-selenocysteine. The rate of beta-elimination may reflect the bond strength of the corresponding C-S, C-Se, and C-Te bond. Bioactivation of Te-phenyl-L-tellurocysteine and its selenium and sulfur analogues by oxidative enzymes was evaluated by measuring NADPH-dependent activation of hepatic mGST and inhibition of EROD. Te-Phenyl-L-tellurocysteine and Se-phenyl-L-selenocysteine displayed strong and time-dependent mGST activation, while S-phenyl-L-cysteine resulted in no significant activation. Te-Phenyl-L-tellurocysteine was also a strong inhibitor of EROD activity. In addition to EROD inhibition, Te-phenyl-L-tellurocysteine was the strongest inhibitor of several human cytochrome P450 isoenzymes followed by Se-phenyl-L-selenocysteine, while S-phenyl-L-cysteine was the weakest inhibitor. Interestingly, Te-phenyl-L-tellurocysteine selectively inhibited cytochrome P450 1A1 directly, which is, for example, responsible for the activation of several procarcinogens. Preliminary cytotoxicity studies with Te-phenyl-L-tellurocysteine in freshly isolated rat hepatocytes showed a time-dependent depletion of GSH and LDH leakage comparable with the relatively nontoxic drug paracetamol, while the selenium and sulfur analogues were nontoxic toward rat hepatocytes. In conclusion, because the chemopreventive and antitumor activities of selenium compounds are thought to be mediated via their selenol metabolites and tellurium compounds might be even more active than selenium compounds, tellurocysteine Te-conjugates might be an interesting novel class of prodrugs for the formation of biologically active tellurols.