Selenocysteine diselenides

For the synthesis of selenocysteine derivatives that are suitable for peptide synthesis essentially two approaches have been used to date (1) conversion of p-chloroalanine 23 or serine-O-tosylate derivatives 24 into the desired selenocysteine derivatives by a nucleophilic displacement reaction with an areneselenol and (2) full reduction of selenocystine and in situ reaction with aryl halides to produce the aryl selenides. 7 25 In this context, reduction of selenocystine in 2 M NaOH with 2-methyl-2-propanethiol for concomitant formation of the mixed selenide/sulfide derivative 5e-(tert-butylsulfanyl)selenocysteine in analogy to the formation of 5-(fett-butylsulfanyl)cysteine 26 fails as a consequence of the difficult reduction of the diselenide with monothiols. 27 ... 

The Se-(4-methoxybenzyl)selenocysteine is obtained by reduction of selenocystine with NaBH4 and in situ reaction with 4-methoxybenzyl chloride. 7 The optimized procedure of Tanaka and Soda 32 is preferentially used for the synthesis of the starting selenocystine, which involves reaction of (1-chloroalanine with a 2.3-fold excess of disodium diselenide in aqueous solution at pH 9. Alternatively, the significantly less selenium demanding synthesis of Stocking et al. 33 is used for the preparation of expensive 77Se-selenocystine, this consists of the reaction of methyl (2R)-2-[(/ert-butoxycarbonyl)amino]-3-iodopropanoate with equivalent amounts of dilithium diselenide. Subsequent conversion of SeC(Mob) into the M -Fmoc derivative 7 and finally into the pentafluorophenyl ester 10 is performed following standard procedures. 

Conditions such as pH, oxidation-reduction potential, and the presence of metal oxides affect the partitioning of the various compounds of selenium in the environment. In general, elemental selenium is stable in soils and is found at low levels in water because of its ability to coprecipitate with sediments. The soluble selenates are readily taken up by plants and converted to organic compounds such as selenomethionine, selenocysteine, dimethyl selenide, and dimethyl diselenide. Selenium is bioaccumulated by aquatic organisms. Very low levels of selenium are found in ambient air. 

The molecular enzymology of this remarkable protein has been extensively reviewed " . Isolated from various sources, the enzyme has an MW of from 76,000 to 92,000 and is composed of four apparently identical subunits of MW from 19,000 to 23,000. Each subunit has a single selenocysteine residue located at position 45 of the amino acid chain . X-Ray crystallographic studies show that this residue lies in an a-helical region and the Se atom is located at the surface of the subunit. The distance between two selenium moieties in the tetramer is too great to allow formation of intramolecular diselenide bonds. 

Naphthylsulphenyl thiocyanate, 2-Cjt)H7 S SCN, is readily converted into di-(2-naphthyl) disulphide with Fe(CO)6-THF at — 70 °C, and has been used for the conversion of JV-benzyloxycarbonyl-selenocysteine diphenylmethyl ester into the 5e-(2-naphthylsulphenyl) derivative, the seleno-sulphide R SSeR , though this disproportionates readily, especially in basic media, and diselenides and disulphides appear in the product mixture for this reason. The Bunte salt, PhCHa-S-SOg" Na+, gives similar results when used in place of the sulphenyl thiocyanate in these studies, and this general route to disulphides - and diselenides, and its variant BuS-S03"Na+ + TolSCl-> BuSSBu + TolSSTol, have been explored more widely. 

Cysteine and selenocysteine residues in proteins are critical components for regulation of a wide range of biological functions. Isolated cysteine and selenocysteine residues located in cavities or clefts within proteins are restrained sterically from forming interchain and/or intrachain disulfide or diselenide bridges. 

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