Title:
NOVEL HIGH-FUNCTIONING ENZYME HAVING ALTERED HUMAN β-HEXOSAMINIDASE B SUBSTRATE SPECIFICITY, AND HAVING PROTEASE RESISTANCE APPLIED THERETO
Document Type and Number:
WIPO Patent Application WO/2014/061735
Kind Code:
A1
Abstract:
Provided is an improved β-subunit of human β-hexosaminidase, having activity derived from a α-subunit of wild-type human β-hexosaminidase, and having resistance to protease. A protein comprising, in the amino acid sequence for a β-subunit of wild-type human β-hexosaminidase, an amino acid sequence in which the 312th-318th amino acids have been substituted, in order, for glycine, serine, glutamic acid, proline, serine, glycine and threonine respectively.
Inventors:
ITO KOJI (JP)
SAKURABA HITOSHI (JP)
TSUJI DAISUKE (JP)
SAKURABA HITOSHI (JP)
TSUJI DAISUKE (JP)
Application Number:
PCT/JP2013/078179
Publication Date:
April 24, 2014
Filing Date:
October 17, 2013
Export Citation:
Assignee:
UNIV TOKUSHIMA (JP)
MEIJI PHARMACEUTICAL UNIVERSITY (JP)
MEIJI PHARMACEUTICAL UNIVERSITY (JP)
International Classes:
C12N15/09; A61K38/46; A61K48/00; A61P25/00; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N9/88
Domestic Patent References:
| WO2010082622A1 | 2010-07-22 | |||
| WO2010082622A1 | 2010-07-22 |
Foreign References:
| JP2012522809A | 2012-09-27 | |||
| JP2002369692A | 2002-12-24 | |||
| JP2012232266A | 2012-11-29 |
Other References:
MARTIN ET AL.: "An inversion of 25 base pairs causes feline Gm2 gangliosidosis varinat 0", EXPERIMENTAL NEUROLOGY, vol. 187, no. 1, May 2004 (2004-05-01), pages 30 - 37, XP004620579
SAGHERIAN ET AL.: "Examination of an area in beta-Hexosaminidase B Homologous to that in Cathepsin D Linked to Lysosomal Targeting", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 179, no. 1, August 1991 (1991-08-01), pages 477 - 481, XP024836355
LEMIEUX ET AL.: "Crystallographic Structure of Human beta-Hexosaminidase A:Interpretation of Tay-Sachs Mutations and Loss of Gm2 Ganglioside Hydrolysis", JOURNAL OF MOLECULAR BIOLOGY, vol. 359, no. 4, 2006, pages 913 - 929, XP024951104
HOU ET AL.: "Characterization of the Glu and Asp Residues in the Active Site of Human beta- Hexosaminidase B", BIOCHEMISTRY, vol. 40, no. 7, February 2001 (2001-02-01), pages 2201 - 2209, XP055251436
BROWN ET AL: "Introduction of the alpha Subunit Mutation Associated with the Bl variant of Tay- Sachs Disease into the beta-Subunit Produces a beta-Hexosaminidase B without Catalytic Activity", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 264, no. 36, 25 December 1989 (1989-12-25), pages 21705 - 21710, XP055251442
TSUJI D ET AL., ANN NEUROL., vol. 69, no. 4, April 2011 (2011-04-01), pages 691 - 701
MATSUOKA K ET AL., MOL THER., vol. 19, no. 6, June 2011 (2011-06-01), pages 1017 - 1024
"Molecular Cloning, A Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
"Current Protocols in Molecular Biology", 1987, JOHN WILEY
See also references of EP 2910632A4
SAGHERIAN ET AL.: "Examination of an area in beta-Hexosaminidase B Homologous to that in Cathepsin D Linked to Lysosomal Targeting", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 179, no. 1, August 1991 (1991-08-01), pages 477 - 481, XP024836355
LEMIEUX ET AL.: "Crystallographic Structure of Human beta-Hexosaminidase A:Interpretation of Tay-Sachs Mutations and Loss of Gm2 Ganglioside Hydrolysis", JOURNAL OF MOLECULAR BIOLOGY, vol. 359, no. 4, 2006, pages 913 - 929, XP024951104
HOU ET AL.: "Characterization of the Glu and Asp Residues in the Active Site of Human beta- Hexosaminidase B", BIOCHEMISTRY, vol. 40, no. 7, February 2001 (2001-02-01), pages 2201 - 2209, XP055251436
BROWN ET AL: "Introduction of the alpha Subunit Mutation Associated with the Bl variant of Tay- Sachs Disease into the beta-Subunit Produces a beta-Hexosaminidase B without Catalytic Activity", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 264, no. 36, 25 December 1989 (1989-12-25), pages 21705 - 21710, XP055251442
TSUJI D ET AL., ANN NEUROL., vol. 69, no. 4, April 2011 (2011-04-01), pages 691 - 701
MATSUOKA K ET AL., MOL THER., vol. 19, no. 6, June 2011 (2011-06-01), pages 1017 - 1024
"Molecular Cloning, A Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
"Current Protocols in Molecular Biology", 1987, JOHN WILEY
See also references of EP 2910632A4
Attorney, Agent or Firm:
HIRAKI Yusuke et al. (JP)
Yusuke Hiraki (JP)
Yusuke Hiraki (JP)
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