Methods for the identification of farnesyltransferase inhibitors

Details Methods for the identification of farnesyltransferase inhibitors Methods for the identification of farnesyltransferase inhibitors

1995-04-27

1999-10-05

Wax, Robert A.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving transferase

435193, 536 232, C12Q 148, C12N 910, C07H 2104

Patent

active

059622431

ABSTRACT:
Disclosed are methods and compositions for the identification of inhibitors of farnesyltransferase enzymes involved in the prenylation of various cellular proteins, including cancer related ras proteins, such as p21.sup.ras, particularly, K-rasB. Enclosed are procedures for using purified farnesyltransferase enzymes and K-rasB proteins in screening protocols for the identification of possible anticancer agents that inhibit the enzyme and thereby prevent prenylation of proteins such as K-RasB.

REFERENCES:
patent: 4677069 (1987-06-01), Chen et al.
patent: 5026554 (1991-06-01), Bartizal et al.
patent: 5043268 (1991-08-01), Stock
patent: 5055487 (1991-10-01), Bartizal et al.
patent: 5104975 (1992-04-01), McCormick et al.
patent: 5185248 (1993-02-01), Barcacid
patent: 5202456 (1993-04-01), Rando
patent: 5234849 (1993-08-01), McCormick et al.
patent: 5238922 (1993-08-01), Graham et al.
patent: 5245061 (1993-09-01), Singh
patent: 5326773 (1994-07-01), de Solms et al.
patent: 5340828 (1994-08-01), Graham et al.
patent: 5352705 (1994-10-01), Deana et al.
patent: 5443956 (1995-08-01), Carney
patent: 5525479 (1996-06-01), Anthony et al.
Lacal et al., "Expression of normal and transforming H-ras genes . . . " (1984) PNAS 81:5305.
Anderegg et al., JBC 263:18236 (1988) Structure of Saccharomyces cerevisiae Mating Hormone a-factor : Identification of S-farnesyl cysteine as a structural component.
Towler et al., PNAS 83:2812 (1986) Protein fatty acid acylation: Enzymatic synthesis of an N-myristoylglycyl peptide.
Towler et al., JBC 262:1030 (1987) Amino terminal processing of proteins by N-myristoylation: Substrate specificity of N-myristoyl transferase.
Clark et al., "Posttranslational Modification of the Ha-ras oncogrne Protein: Evidence for a Third Class of Protein Carboxyl Methyltransferases," Proc. Natl. Acad. Sci. USA, 85:4643-4647, 1988.
Hancock et al., "All ras Proteins are Polyisoprenylated but Only come Are Palmitoylated," Cell, 57:1167-77, 1989.
Schafer et al., "Genetic and Pharmacological Suppression of Oncogenic Mutatins in RAS Genes of Yeast and Humans," Science, 245:379-385, 1989.
BOS, "ras Oncogenes in Human Cancer: A Review," Cancer Research, 49:4682-4689, 1989.
Lowy et al., "New Clue to Ras Lipid Glue," Nature, 341:384-85, 1989.
Casey et al., "p21ras Is Modified by a Farnesyl Isoprenoid," Proc. Natl. Acad. Sci. USA, 86:8323-8327, 1989.
Goldstein et al., "Regulation of the Mevalonate Pathway," Nature, 343:425-430, 1990.
Reiss et al., Inhibition of Purified p21.sup.ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptidesanne et al. Cell, 62:81-88, 1990.
Schaber et al., "Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase," J. Biolog. Chem., 265(25):14701-14704, 1990.
Manne et al., "Identification and Preliminary Characterization of Protein-Cysteine Farnesyltransferase," Proc. Natl. Acad. Sci. USA, 87:7541-7545, 1990.
Reiss et al., "Sequence Requirement for Peptide Recognition by Rat Brain p21.sup.ras Protein Farnesyltransferase," Proc. Natl. Acad. Sci. USA, 88:732-736, 1991.
Chen, et al., "cDNA Cloning and Expression of the Peptide-Binding .beta. Subunit of Rat p21.sup.ras Farnesyltransferase, the Counterpart of Yeast DPR1/RAM1," Cell, 66:327-334, 1991.
Goldstein, et al., "Nonfarnesylated Tetrapeptide Inhibitors of Protein Farnesyltransferase," J. Biol. Chem., 266(24):15575-15578, 1991.
Goodman, et al., "Structure and Expression of Yeast DPR1, a Gene Essential for the Processing and Intracellular Localization of ras Proteins," Yeast, 4:271-281, 1988.
Goodman, et al., "Mutants of Saccharomyces cerevisiae Defective in the Frnesylation of Ras Proteins," Proc. Natl. Acad. Sci., 87:9665-9669, 1990.
Schaber, et al., "Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase," Chem. Abstr., 114:302, Abstract # 38170r, 1991.
Kim, et al., "Prenylation of Mammalian Ras Protein in Xenopus Oocytes," Chem. Abstr., 114:373, Abstract # 3711r, 1991.
Kohl et al., "Structural Homology Among Mammalian and Saccharomyces cerevisiae Isoprenyl-protein Transferases," J. Biol. Chem., 266(28):18884-18888, 1991.
He et al., "RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins," PNAS, 88:11373-11377, 1991.
International Search Report mailed Dec. 9, 1991.
Reiss, et al., "Divalent Cation and Prenyl Pyrophosphate Specificites of the Protein Farnesyltransferase from Rat Brain, a Zinc Metalloenzyme," J. Biol. Chem., 267:6403-6408, 1992. Published in USA.
Seabra, et al., "Protein Farnesyltransferase and Geranylgeranyltransferase Share a Common .alpha. Subunit," Cell, 65:429-434, 1991. Published in USA.
Reiss, et al., "Purification of ras Farnesyl:Protein Transferase," Methods: A Companion to Methods in Enzymology, 1(3):241-245, 1990. Published in USA.
Nancy E. Kohl, et al., "Selective Inhibition of ras-Dependent Transformation by a Farnesyltransferase Inhibitor", Science, 260:1934-1937 (1993).
International Search Report, mailed Jan. 24, 1994.
Barbacid, "ras Genes," Ann. Rev. Biochem, 56:779-827, 1987.
Capon et al., "Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations," Nature 304:507-513, 1983.
Chen et al., "Cloning and expression of a cDNA encoding the .alpha. subunit of rat p21.sup.ras protein farnesyltransferase," Proc. Natl. Acad. Sci. USA, 88:11368-11372, 1991.
Cremers et al., "REP-2, a Rab Escort Protein Encoded by the Choroideremia-like Gene," The Journal of Biological Chemistry, 269(3): 2111-2117, 1994.
James et al., "Benzodiazepine Peptidomimetics: Potent Inhibitors of Ras Farnesylation in Animal Cells," Science, 260:1937-1942, 1993.
James et al., "Benzodiazepine Peptidomimetic BZA-5B Interrupts the MAP Kinase Activation Pathway in H-Ras-transformed Rat-1 Cells, but Not in Untransformed Cells," TheJournal of Biological Chemistry, 269(44):27705-27714, 1994.
McCoy et al., "Human Colon Carcinoma Ki-ras2 Oncogene and Its Corresponding Proto-Oncogene," Molecular and Cellular Biology, 4(8):1577-1582, 1984.
McGrath et al., "Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene," Nature, 304:501-506, 1983.
Shimizu et al., "Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1," Nature, 304:497-500, 1983.
Yokoyama et al., "A protein geranylgeranyltransferase from bovine brain: Implications for protein prenylation specificity," Proc. Natl. Acad. Sci. USA, 88:5302-5306, 1991.
Zhang et al., "cDNA Cloning and Expression of Ray and Human Protein Geranylgeranyltransferase Type-I," The Journal of Biological Chemistry, 269(5):3175-3180, 1994.
James et al., "Polylysine and CVIM Sequences of K -RasB Dictate Specificity of Prenylation and Confer Resistance to Benzodiazepine Peptidomimetic in vitro," J. Biol. Chem, 270(11):6221-6226, 1995.
Reiss et al., "Purification of Ras Farnesyl: Protein Transferase," Methods, 1(3):241-245, 1990.
PCT Search Report mailed Oct. 12, 1996.

Affiliated with

Also associated with

Rating

Methods for the identification of farnesyltransferase inhibitors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods for the identification of farnesyltransferase inhibitors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for the identification of farnesyltransferase inhibitors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1170117