Diselenides as proxies of disulfides in cystine-rich peptides

摘要

The strongly reducing redox potential and isosteric character of selenocysteine compared to cysteine allows to install in correct position a diselenide bridge when a pair of natively-crossbridged cysteine residues are replaced synthetically by a pair of selenocysteines. This regioselective formation of the diselenide bond represents a powerful strategy for directing oxidative folding of peptides containing multiple disulfide bonds into the native diselenide/disulfide framework by reducing the number of possible disulfide isomers and thus enhancing folding efficiency. This is well documented by the successful synthesis of conotoxins, most notably of α-conotoxihs with two disulfide bonds, but also of 3-disulfide-bridged μ- and ω-conotoxins which generally show a low propensity to form in satisfactory yields by air oxidation of the multiple cysteine-precursors the native disulfide isomer.