Integrated process for the enzymatic synthesis of the octapeptide PhAcCCK-8.
A process for the enzymatic synthesis of PhAcCCK-8 is presented. The CCK-8 (CCK(26-33)) peptide fragment is the minimum sequence with biological activity of the cholecystokinin hormone. A synthetic convergent strategy has been developed starting from amino acid derivatives as raw materials, employing proteases as biocatalysts for each peptide coupling. The enzymes have been immobilized by deposition onto solid supports in order to be employed in organic media at low water activity. N-terminal protecting groups such as PhAc, which can be introduced and removed enzymatically, have been employed. The synthesis process has been set up at preparative level with focus in the integration of reaction and separation steps with an overall yield of 15%.
Fité
Mercè
M
Unitat de Biocatàlisi Aplicada Associada al IIQAB (UAB-CSIC), Departament d'Enginyeria Química, Escola Tècnica Superior d'Enginyeria, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
Clapés
Pere
P
López-Santín
Josep
J
Benaiges
M Dolors
MD
Caminal
Glòria
G
D001426:Bacterial Proteins / Q000378:metabolism; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000378:metabolism; D004800:Enzymes, Immobilized / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000302:isolation & purification; D012844:Sincalide / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000302:isolation & purification; D012997:Solvents
D001426:Bacterial Proteins; D004800:Enzymes, Immobilized; D009842:Oligopeptides; D012997:Solvents; C044201:cholecystokinin (26-33); D010450:Endopeptidases; D012844:Sincalide