Methods and compositions for the identification, characterizatio

Details Methods and compositions for the identification, characterizatio Methods and compositions for the identification, characterizatio

1992-08-24

2000-07-04

Davenport, Avis M.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 17, 514128, 514183, 514365, 514520, 514534, 530330, 530329, 435 691, 435107, 435228, A61K 3800, A61K 3802, C07K 500, C07K 700

Patent

active

060839171

ABSTRACT:
Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian protein farnesyltransferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. One protein farnesyltransferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. Also disclosed are methods and compositions for the preparation of farnesyltransferase by recombinant means, following the molecular cloning and co-expression of its two subunits, for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21.sup.ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme. The most potent inhibitors are ones in which phenylalanine occurs at the third position of a tetrapeptide whose amino terminus is cysteine.

REFERENCES:
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), Barbacid
patent: 5202456 (1993-04-01), Rando
patent: 5234839 (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.
Reiss, et al., "Divalent Cation and Prenyl Pyrophosphate Specificities 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.
Chen, et al., Cell, 66:327-334, 1991.
Goldstein, et al., J Biol Chem, 266(24):15575-15578, 1991.
Goodman, et al., Yeast, 4:271-281, 1988.
Goodman, et al., Proc. Natl. Acad. Sci., 87:9665-9669, 1990.
Schaber, et al., Chem. Abstr., 114:302, Abstract #38170r, 1991.
Kim, et al., Chem. Abstr., 114:373, Abstract #3711r, 1991.
Kohl et al., J. Biol. Chem., 266(28):18884-18888, 1991.
He et al., PNAS, 88:11373-11377, 1991.
International Search Report.
Clarke et al., Proc. Natl. Acad. Sci. USA, 85:4643-4647, 1988.
Hancock et al., Cell, 57:1167-77, 1989.
Schafer et al., Science, 245:379-385, 1989.
Bos, Cancer Research, 49:4682-4689, 1989.
Lowy et al., Nature, 341:384-85, 1989.
Casey et al., Proc. Natl. Acad. Sci. USA, 86:8323-8327, 1989.
Goldstein et al., Nature, 343:425-430, 1990.
Schaber et al., Journal of Biol. Chem., 265:14701-14704, 1990.
Manne et al., Proc. Natl. Acad. Sci. USA, 87:7541-7545, 1990.
Reiss et al., Cell, 62:81-88, 1990.
Reiss et al., Proc. Natl. Acad. Sci. USA, 88:732-736, 1991.

Affiliated with

Also associated with

Rating

Methods and compositions for the identification, characterizatio 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 and compositions for the identification, characterizatio, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for the identification, characterizatio will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1486643