Title:
PROCESS FOR PRODUCTION OF PEPTIDE THIOESTER
Document Type and Number:
WIPO Patent Application WO/2010/150730
Kind Code:
A1
Abstract:
Provided is a novel process for chemically converting a peptide chain into a peptide thioester. The inventors paid attention to the cysteine residue of a peptide chain. As a result, the following has been found. When a –C(=X)-R1 group is introduced to the thiol group of the cysteine residue and then the resulting peptide is reacted with a compound having a leaving group represented by the formula: -NH-C(=Y)NHR3 in an organic solvent, the -NH-C(=Y)NHR3 group binds via addition reaction to the carboxyl group of the N-terminal-side peptide bond of the cysteine residue, whereby the peptide bond is cleaved and the C-terminal-side peptide fragment is cut off. Further, when the resulting peptide chain having the –NH-C(=Y)NHR3 group is reacted with a thiol in a buffer solution, a thiol exchange reaction occurs, namely, the thiol group of the thiol binds to the carbonyl carbon to which the –NH-C(=Y)NHR3 group has bound, whereby the –NH-C(=Y)NHR3 group is eliminated. Thus, the conversion into a peptide thioester is attained.
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Inventors:
KAJIHARA YASUHIRO (JP)
OKAMOTO RYO (JP)
SAKAMOTO IZUMI (JP)
ISHII KAZUYUKI (JP)
OKAMOTO RYO (JP)
SAKAMOTO IZUMI (JP)
ISHII KAZUYUKI (JP)
Application Number:
PCT/JP2010/060443
Publication Date:
December 29, 2010
Filing Date:
June 21, 2010
Export Citation:
Assignee:
OTSUKA CHEMICAL CO LTD (JP)
KAJIHARA YASUHIRO (JP)
OKAMOTO RYO (JP)
SAKAMOTO IZUMI (JP)
ISHII KAZUYUKI (JP)
KAJIHARA YASUHIRO (JP)
OKAMOTO RYO (JP)
SAKAMOTO IZUMI (JP)
ISHII KAZUYUKI (JP)
International Classes:
C07K1/06; C07K7/06; C07K14/00; C12P21/02
Domestic Patent References:
| WO2007043615A1 | 2007-04-19 | |||
| WO2007114454A1 | 2007-10-11 | |||
| WO1996034878A1 | 1996-11-07 | |||
| WO2007114454A1 | 2007-10-11 |
Other References:
BRASK J. ET AL.: "Fmoc solid-phase synthesis of peptide thioesters by masking as trithioortho esters", ORG. LETT., vol. 5, no. 16, 2003, pages 2951 - 2953, XP008149114
JOHNSON EC. ET AL.: "Insights into the mechanism and catalysis of the native chemical ligation reaction", J. AM. CHEM. SOC., vol. 128, no. 20, 2006, pages 6640 - 6646, XP008149115
OKAMOTO R. ET AL.: "Efficient substitution reaction from cysteine to the serine residue of glycosylated polypeptide: repetitive peptide segment ligation strategy and the synthesis of glycosylated tetracontapeptide having acid labile sialyl-T(N) antigens", J. ORG. CHEM., vol. 74, no. 6, May 2009 (2009-05-01), pages 2494 - 2501, XP055008165
INGENITO ET AL., J. AM. CHEM. SOC., vol. 121, 1999, pages 11369 - 11374
SCHWARTZ ET AL., CHEMCOMMUN, 2003, pages 2087 - 2090
MUIR, ANNU. REV. BIOCHEM., vol. 72, 2003, pages 249 - 289
STARK GR, METHODS OF ENZYMOLOGY, vol. 47, 1977, pages 129 - 132
NAKAGAWA ET AL., J. AM. CHEM. SOC., vol. 116, 1994, pages 5513 - 5514
SOLA ET AL., J. CHEM. SOC. CHEM. COMMUN., 1993, pages 1786 - 1788
PASCAL ET AL., TETRAHEDRON LETTERS, vol. 35, no. 34, 1994, pages 6291 - 6294
See also references of EP 2450364A4
JOHNSON EC. ET AL.: "Insights into the mechanism and catalysis of the native chemical ligation reaction", J. AM. CHEM. SOC., vol. 128, no. 20, 2006, pages 6640 - 6646, XP008149115
OKAMOTO R. ET AL.: "Efficient substitution reaction from cysteine to the serine residue of glycosylated polypeptide: repetitive peptide segment ligation strategy and the synthesis of glycosylated tetracontapeptide having acid labile sialyl-T(N) antigens", J. ORG. CHEM., vol. 74, no. 6, May 2009 (2009-05-01), pages 2494 - 2501, XP055008165
INGENITO ET AL., J. AM. CHEM. SOC., vol. 121, 1999, pages 11369 - 11374
SCHWARTZ ET AL., CHEMCOMMUN, 2003, pages 2087 - 2090
MUIR, ANNU. REV. BIOCHEM., vol. 72, 2003, pages 249 - 289
STARK GR, METHODS OF ENZYMOLOGY, vol. 47, 1977, pages 129 - 132
NAKAGAWA ET AL., J. AM. CHEM. SOC., vol. 116, 1994, pages 5513 - 5514
SOLA ET AL., J. CHEM. SOC. CHEM. COMMUN., 1993, pages 1786 - 1788
PASCAL ET AL., TETRAHEDRON LETTERS, vol. 35, no. 34, 1994, pages 6291 - 6294
See also references of EP 2450364A4
Attorney, Agent or Firm:
NANJO, Masahiro et al. (JP)
Masahiro Nanjo (JP)
Masahiro Nanjo (JP)
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