NEW APPROACHES TO THE SYNTHESIS OF CYSTINE PEPTIDES USING N-IODOSUCCINIMIDE IN THE CONSTRUCTION OF DISULFIDE BRIDGES

N-Halosuccinimides have been found to convert cysteine, S-(acetamidome thyl)-, S-(p-methoxybenzyl)-, or S-(p-methylbenzyl)cysteine into cysti ne. N-Iodosuccinimide, the mildest reagent among N-halosuccinimides, i s applied successfully in the synthesis of (Arg8)-vasopressin and oxyt ocin by a fully automated process of solid-phase peptide synthesis or by cyclizing the released thiol peptides in DMF-CH2Cl2. These simple a nd 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 processes of stepwise addi tion of Boc-amino acids and controlled stepwise formation of the disul fide bonds. These new approaches may be useful in the synthesis of lar ger and more complex cystine peptides.