R. Soll et Ag. Beck-sickinger, On the synthesis of orexin A: A novel one-step procedure to obtain peptides with two intramolecular disulphide bonds, J PEPT SCI, 6(8), 2000, pp. 387-397
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.