Title:
INHIBITORS OF PROTEINS FROM THE RHO-GEF FAMILY
Document Type and Number:
WIPO Patent Application WO2003099778
Kind Code:
A3
Abstract:
The present invention relates to the use of an aptamer library for determining inhibitors of any one of the proteins from the Rho-GEFs family, by an appropriate screening process. The present invention also relates to a process for determining inhibitors of any one of the proteins from the Rho-GEFs family, comprising a step of contacting said protein for which an inhibitor is sought with the peptides from an aptamer library, a step of recovering a first group of peptides which specifically bind to said protein, particularly to the catalytic domain of the GEF region of said protein, a step of recovering, among the first group of peptide as mentioned above, the peptide which specifically inhibits the in vitro exchange activity of said protein towards any one of the proteins from the Rho-GTPases family, as determined for example in the GEF assay, and a step of testing the peptide as mentioned above for its capacity to inhibit in intact cells the activity of the Rho-GEF on the appropriate GTPase, using for example the GTPase activity assay.
Inventors:
DEBANT ANNE (FR)
SCHMIDT SUSANNE (FR)
SCHMIDT SUSANNE (FR)
Application Number:
PCT/EP2003/005485
Publication Date:
September 16, 2004
Filing Date:
May 26, 2003
Export Citation:
Assignee:
CENTRE NAT RECH SCIENT (FR)
DEBANT ANNE (FR)
SCHMIDT SUSANNE (FR)
DEBANT ANNE (FR)
SCHMIDT SUSANNE (FR)
International Classes:
C07K14/00; C07K14/82; G01N33/68; A61K38/00; (IPC1-7): C07K14/00; C12N15/00; A61K38/16
Foreign References:
| US6238881B1 | 2001-05-29 |
Other References:
SCHMIDT S ET AL: "FUNCTIONAL STUDY OF THE RHO-GEF DOMAINS OF TRIO BY SELECTING NOVEL PEPTIDE INHIBITORS", April 2000, BIOLOGY OF THE CELL, CONGRESS OF THE FRENCH SOCIETY OF CELL BIOLOGY, PARIS, FRANCE, VOL. 92, NR. 2, PAGE(S) 172, ISSN: 0248-4900, XP001145963
COLAS P ET AL: "GENETIC SELECTION OF PEPTIDE APTAMERS THAT RECOGNIZE AND INHIBIT CYCLIN-DEPENDENT KINASE 2", 11 April 2000, NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, VOL. 380, PAGE(S) 548-550, ISSN: 0028-0836, XP000904376
DATABASE SWISSPROT [online] 21 July 1986 (1986-07-21), XP002231905, Database accession no. P00274
DATABASE SWISSPROT [online] 4 July 2000 (2000-07-04), XP002231906, Database accession no. AAF33471
DATABASE SWISSPROT [online] 1 March 2002 (2002-03-01), XP002231907, Database accession no. Q8XAT2
DATABASE EMBL [online] 25 November 2001 (2001-11-25), XP002231908, Database accession no. AC102676
ESTRACH S ET AL: "THE HUMAN RHO-GEF TRIO AND ITS TARGET GTPASE RHOG ARE INVOLVED IN THE NGF PATHWAY, LEADING TO NEURITE OUTGROWTH", 19 February 2002, CURRENT BIOLOGY, ELSEVIER SCIENCE LTD., VOL. 12, PAGE(S) 307-312, ISSN: 1960-9822, XP001145960
GEYER C R AND BRENT R: "SELECTION OF GENETIC AGENTS FROM RANDOM PEPTIDE APTAMER EXPRESSION LIBRARIES", METHODS ENZYMOL, vol. 328, 2000, pages 171 - 208, XP001157025
"HOMOLOGY IN PROTEINS AND NUCLEIC ACIDS: A TERMINOLOGY MUDDLE AND A WAY OUT OF IT", 1987, CELL, CELL PRESS, CAMBRIDGE, NA, US, VOL. 50, PAGE(S) 667, ISSN: 0092-8674, XP002913075
COLAS P ET AL: "GENETIC SELECTION OF PEPTIDE APTAMERS THAT RECOGNIZE AND INHIBIT CYCLIN-DEPENDENT KINASE 2", 11 April 2000, NATURE, MACMILLAN JOURNALS LTD. LONDON, GB, VOL. 380, PAGE(S) 548-550, ISSN: 0028-0836, XP000904376
DATABASE SWISSPROT [online] 21 July 1986 (1986-07-21), XP002231905, Database accession no. P00274
DATABASE SWISSPROT [online] 4 July 2000 (2000-07-04), XP002231906, Database accession no. AAF33471
DATABASE SWISSPROT [online] 1 March 2002 (2002-03-01), XP002231907, Database accession no. Q8XAT2
DATABASE EMBL [online] 25 November 2001 (2001-11-25), XP002231908, Database accession no. AC102676
ESTRACH S ET AL: "THE HUMAN RHO-GEF TRIO AND ITS TARGET GTPASE RHOG ARE INVOLVED IN THE NGF PATHWAY, LEADING TO NEURITE OUTGROWTH", 19 February 2002, CURRENT BIOLOGY, ELSEVIER SCIENCE LTD., VOL. 12, PAGE(S) 307-312, ISSN: 1960-9822, XP001145960
GEYER C R AND BRENT R: "SELECTION OF GENETIC AGENTS FROM RANDOM PEPTIDE APTAMER EXPRESSION LIBRARIES", METHODS ENZYMOL, vol. 328, 2000, pages 171 - 208, XP001157025
"HOMOLOGY IN PROTEINS AND NUCLEIC ACIDS: A TERMINOLOGY MUDDLE AND A WAY OUT OF IT", 1987, CELL, CELL PRESS, CAMBRIDGE, NA, US, VOL. 50, PAGE(S) 667, ISSN: 0092-8674, XP002913075
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