Inhibitors of geranylgeranyl-protein transferase

Details Inhibitors of geranylgeranyl-protein transferase Inhibitors of geranylgeranyl-protein transferase

1994-01-31

1995-11-28

Warden, Jill

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 19, 530331, 562428, 562556, 560 9, 560 16, 560147, A61K 3800, C07K 500, C07K 700, C07K 1700

Patent

active

054708320

ABSTRACT:
The compounds disclosed am analogs of the CAAX motif of proteins that can be modified by geranylgeranylation in vivo that selectively inhibit the geranylgeranylation of several proteins. The relatively poor activity of the compounds against the farnesyl protein transferase, which modifies several proteins important in cellular replication, allows the use of the compounds of the instant invention to treat diseases which which am regulated by the function of a geranylgeranylated protein, such as certain cancers and inflammatory diseases. Further contained in this invention are chemotherapeutic compositions containing these geranylgeranyl protein transfcrase type I inhibitors and methods for their production.

REFERENCES:
patent: 5238922 (1993-08-01), Graham et al.
Kohl et al. Science vol. 260 p. 1834 (1993).
Brown, M. S. and Goldstein, J. L., Mad Bet for Rab, (1993), Nature, 366, pp. 14-15.
Casey, P. J., Biochemistry of protein prenylation (1992), Journal of Lipid Research, 33, pp. 1731-1740.
Casey, P. J., et al., Enzymatic modification of proteins with a geranylgeranyl isoprenoid, (1991), Proc. Natl. Acad. Sci., USA, Biochemistry, 88, pp. 8631-8635.
Clarke, S., Protein Isoprenylation and Methylation At Carboxyl-Terminal Cysteine Residues, (1992), Annu. Rev. Biochem., 61, pp. 355-386.
Cox, A. D. and Der, CD. J., The Ras/Cholesterol Connection: Implications for Ras Oncogenicity, (1992), Critical Reviews in Oncogenesis, 3(4), pp. 365-400.
Gibbs, J. B., Ras C-Terminal Processing Enzymes--New Drug Targets?, (1991), Cell, 65, pp. 1-4.
Menard, L., et al., Rac1, a low-molecular-mass GTP-binding-protein with high intrinsic GTPase activity and distinct biochemical properties, (1992), Eur. J. Biochem., 206, pp. 537-546.
Moomaw, J. F. and Casey, P. J., Mammalian Protein Geranylgeranyltransferase, (1992), The Journal of Biological Chemistry, 267, No. 24, (Issue of Aug. 25), pp. 17438-17443.
Moores, S. L., et al., Sequence Dependence of Protein Isoprenylation, (1991), The Journal of Biological Chemistry, 266, No. 22, (Issue of Aug. 5), pp. 14603-14610.
Newmann, C. M. H. and Magee, A. I., Posttranslational processing of the ras superfamily of small GTP-binding proteins, (1993), Biochimica et Biophysica Acta. 1155, pp. 79-96.
Ridley, A. J. and Hall, A., The Small GTP-Binding Protein rho Regulates the Assembly of Focal Adhesions and Actin Stress Fibers in Response to Growth Factors, (1992), Cell, 70, pp. 389-399.
Ridley, A. J., et al., The Small GTP-Binding Protein rac Regulates Growth Factor-Induced Membrane Ruffling, (1992), Cell, 70, pp. 401-410.
Sato, Y., et al., High-performance size-exclusion chromatography and molar mass measurement by low-angle laser light scattering of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particles, (1990), Journal of chromatography, 507, pp. 25-31.
Seabra, M. C., et al., Rab Geranylgeranyl Transferase, (1992) The Journal of Biological Chemistry, 267, No. 20 (Issue of Jul. 15), pp. 14497-14503.
Schulman, C. A., et al., Production of hepatitis B surface antigen (PreS2+S) by high-cell density cultivations of a recombinant yeast, (1991), Journal of Biotechnology 21, pp. 109-126.
Yokoyama, K., et al., A protein geranylgeranyltransferase from bovine brain: Implications for protein prenylation specificity, (1991), Proc. Natl. Acad. Sci., USA, 88, Biochemistry, pp. 5302-5306.
Reiss, Y., et al., Sequence requirement for peptide recognition by rat brain p21ras protein farnesyltransferase, (1991), Proc. Natl. Acad. Sci. USA, Biochemistry, 88, pp. 732-736.

Affiliated with

Also associated with

Rating

Inhibitors of geranylgeranyl-protein transferase does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Inhibitors of geranylgeranyl-protein transferase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Inhibitors of geranylgeranyl-protein transferase will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2013716