New Approaches to the Synthesis of Cystine Peptides Using N-Iodosuccinimide in the Construction of Disulfide Bridges

Article abstract of DOI:10.1021/jo00063a017

N-Halosuccinimides have been found to convert cysteine, S-(acetamidomethyl)-, S-(p-methoxybenzyl)-, or S-(p-methylbenzyl)cysteine into cystine.N-Iodosuccinimide, the mildest reagent among N-halosuccinimides, is applied successfully in the synthesis of (Arg⁸)-vasopressin and oxytocin by a fully automated process of solid-phase peptide synthesis or by cyclizing the released thiol peptides in DMF-CH2Cl2.These simple and synthetically useful methods have led to the fully automated solid-phase synthesis of (Cys⁵,Cys¹²)human growth hormone releasing factor (1-29)-NH2 and apamin based on the combined process of stepwise addition of Boc-amino acids and controlled stepwise formation of the disulfide bonds.These new approaches may be useful in the synthesis of larger and more complex cystine peptides.