On the synthesis of orexin A: A novel one-step procedure to obtain peptides with two intramolecular disulphide bonds

An efficient strategy for the synthesis of orexin A, a recently discovered neuropeptide with two intramolecular disulphide bonds, was developed. Four different methods for the synthesis of peptides containing two disulphide b onds were compared and optimized with respect to reaction time, purity of t he crude peptide and yield of the purified peptide. A new one-step cyclizat ion method in solution is presented for fast, easy and high yield synthesis of orexin A, based on iodine oxidation in acetic acid/water and S-acetamid omethyl (S-Acm) and S-trityl (S-M) for side-chain protection of cysteine. D isulphide formation without selective side-chain protection leads to the fo rmation of different mono- and bicyclic configurations of orexin A. These d ata stress the requirement of selective cysteine side-chain protection in t he synthesis of orexin A. Copyright (C) 2000 European Peptide Society and J ohn Wiley & Sons. Ltd.