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Total Enzymatic Synthesis of the Cholecystokinin Octapeptide (CCK‐8)
Author(s) -
Joshi Rajendra,
Meng Liping,
Eckstein Heiner
Publication year - 2008
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200890128
Subject(s) - chemistry , cholecystokinin , tripeptide , enzyme , trypsin , stereochemistry , chymotrypsin , protecting group , peptide , biochemistry , organic chemistry , receptor , alkyl
The enzymatic synthesis of the cholecystokinin octapeptide (CCK‐8) is reported. The target octapeptide CCK‐8 is the minimum active sequence with the same biological activity as naturally occurring cholecystokinin and is a potential therapeutic agent in the control of gastrointestinal function as well as a drug candidate for the treatment of epilepsy and obesity. The protected CCK‐8 was obtained by incubation of Bz‐Arg‐Asp(OEt)‐Tyr‐Met‐OAl and Gly‐Trp‐Met‐Asp(OMe)‐Phe‐NH 2 with immobilized α ‐chymotrypsin. The Bz‐Arg group was used as an N‐terminal protecting group in the synthesis of the tripeptide fragment. The protected CCK‐8 was treated with trypsin to remove the Bz‐Arg group successfully. Free or immobilized enzymes were used as catalysts. The effect of the acyl donor ester structure, the C( α ) protecting group of the nucleophile, reaction media, enzyme, and the carrier of the enzymes on the outcome of the coupling reaction was studied.