Title:
MUTATIONS OF THE MDR1 P-GLYCOPROTEIN THAT IMPROVE ITS ABILITY TO CONFER RESISTANCE TO CHEMOTHERAPEUTIC DRUGS
Document Type and Number:
WIPO Patent Application WO2002010205
Kind Code:
A3
Abstract:
The present invention provides mutant P-glycoprotein polypeptides that confer increased resistance to certain chemotherapeutic drugs relative to wild-type P-glycoprotein or P-glycoprotein having a glycine to valine substitution at position 185, and nucleic acid molecules encoding the same. The invention also provides antibodies that specifically bind mutant P-glycoproteins. The invention further provides methods for the diagnosis and treatment of conditions associated with P-glycoprotein-mediated multidrug resistance.
Inventors:
RUTH ADAM (US)
RONINSON IGOR (US)
RONINSON IGOR (US)
Application Number:
PCT/US2001/024560
Publication Date:
June 19, 2003
Filing Date:
August 01, 2001
Export Citation:
Assignee:
UNIV ILLINOIS (US)
RUTH ADAM (US)
RONINSON IGOR (US)
RUTH ADAM (US)
RONINSON IGOR (US)
International Classes:
C07K14/705; C07K16/28; C12Q1/68; C12Q1/6886; A61K38/00; (IPC1-7): C12N15/00
Foreign References:
| US5830697A | 1998-11-03 |
Other References:
CURRIER STEPHEN J ET AL: "Identification of residues in the first cytoplasmic loop of P-glycoprotein involved in the function of chimeric human MDR1-MDR2 transporters.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 267, no. 35, 1992, pages 25153 - 25159, XP002227979, ISSN: 0021-9258
RONINSON I B ET AL: "ISOLATION OF ALTERED-FUNCTION MUTANTS AND GENETIC SUPPRESSOR ELEMENTS OF MULTIDRUG TRANSPORTER P-GLYCOPROTEIN BY EXPRESSION SELECTION FROM RETROVIRAL LIBRARIES", METHODS IN ENZYMOLOGY, ACADEMIC PRESS INC, SAN DIEGO, CA, US, vol. 292, 1998, pages 225 - 248, XP001105795, ISSN: 0076-6879
SAFA A R ET AL: "MOLECULAR BASIS OF PREFERENTIAL RESISTANCE TO COLCHICINE IN MULTIDRUG-RESISTANT HUMAN CELLS CONFERRED BY GLY-185-VAL-185 SUBSTITUTION IN P GLYCOPROTEIN", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 87, no. 18, September 1990 (1990-09-01), pages 7225 - 7229, XP002214152, ISSN: 0027-8424
RUTH ADAM ET AL: "Coordinate changes in drug resistance and drug-induced conformational transitions in altered-function mutants of the multidrug transporter P-glycoprotein", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 40, no. 14, 10 April 2001 (2001-04-10), pages 4332 - 4339, XP002214153, ISSN: 0006-2960
LOO T W ET AL: "MUTATIONS TO AMINO ACIDS LOCATED IN PREDICTED TRANSMEMBRANE SEGMENT 6 (TM6) MODULATE THE ACTIVITY AND SUBSTRATE SPECIFICITY OF HUMAN P-GLYCOPROTEIN", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 33, no. 47, 29 November 1994 (1994-11-29), pages 14049 - 14057, XP001105710, ISSN: 0006-2960
LOO TIP W ET AL: "Functional consequences of glycine mutations in the predicted cytoplasmic loops of P-glycoprotein", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 269, no. 10, 11 March 1994 (1994-03-11), pages 7243 - 7248, XP002214154, ISSN: 0021-9258
TAGUCHI YOSHITOMO ET AL: "Alteration of substrate specificity by mutations at the His-61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 36, no. 29, 1997, pages 8883 - 8889, XP002214155, ISSN: 0006-2960
RONINSON I B ET AL: "ISOLATION OF ALTERED-FUNCTION MUTANTS AND GENETIC SUPPRESSOR ELEMENTS OF MULTIDRUG TRANSPORTER P-GLYCOPROTEIN BY EXPRESSION SELECTION FROM RETROVIRAL LIBRARIES", METHODS IN ENZYMOLOGY, ACADEMIC PRESS INC, SAN DIEGO, CA, US, vol. 292, 1998, pages 225 - 248, XP001105795, ISSN: 0076-6879
SAFA A R ET AL: "MOLECULAR BASIS OF PREFERENTIAL RESISTANCE TO COLCHICINE IN MULTIDRUG-RESISTANT HUMAN CELLS CONFERRED BY GLY-185-VAL-185 SUBSTITUTION IN P GLYCOPROTEIN", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 87, no. 18, September 1990 (1990-09-01), pages 7225 - 7229, XP002214152, ISSN: 0027-8424
RUTH ADAM ET AL: "Coordinate changes in drug resistance and drug-induced conformational transitions in altered-function mutants of the multidrug transporter P-glycoprotein", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 40, no. 14, 10 April 2001 (2001-04-10), pages 4332 - 4339, XP002214153, ISSN: 0006-2960
LOO T W ET AL: "MUTATIONS TO AMINO ACIDS LOCATED IN PREDICTED TRANSMEMBRANE SEGMENT 6 (TM6) MODULATE THE ACTIVITY AND SUBSTRATE SPECIFICITY OF HUMAN P-GLYCOPROTEIN", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 33, no. 47, 29 November 1994 (1994-11-29), pages 14049 - 14057, XP001105710, ISSN: 0006-2960
LOO TIP W ET AL: "Functional consequences of glycine mutations in the predicted cytoplasmic loops of P-glycoprotein", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 269, no. 10, 11 March 1994 (1994-03-11), pages 7243 - 7248, XP002214154, ISSN: 0021-9258
TAGUCHI YOSHITOMO ET AL: "Alteration of substrate specificity by mutations at the His-61 position in predicted transmembrane domain 1 of human MDR1/P-glycoprotein", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, PA, US, vol. 36, no. 29, 1997, pages 8883 - 8889, XP002214155, ISSN: 0006-2960
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