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 bonds were compared and optimized with respect to reaction time, purity of the crude peptide and yield of the purified peptide. A new one-step cyclization 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-acetamidomethyl (S-Acm) and S-trityl (S-Trt) for side-chain protection of cysteine. Disulphide formation without selective side-chain protection leads to the formation of different mono- and bicyclic configurations of orexin A. These data stress the requirement of selective cysteine side-chain protection in the synthesis of orexin A.
Söll
R
R
Department of Applied Biosciences, Swiss Federal Institute of Technology, Zurich.
Beck-Sickinger
A G
AG
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000138:chemical synthesis* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D000068797:Orexins
D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins