Title:
COMPOUNDS FOR INHIBITION OF PROTEIN METHYLATION
Document Type and Number:
WIPO Patent Application WO1992018465
Kind Code:
A1
Abstract:
The invention features a compound of the formula W-Y-Q-Z or W-Y-Zwherein W is a farnesyl group, a geranylgeranyl group, a substituted farnesyl group or a substituted geranylgeranyl group; Y is (1); Q is (2), wherein n = 1, 2, 3, 4, 5, or 6; each of T1'? ... Tn'? and T1'? ... Tn'? is independently: Fl, Br, -NHCOCH3?, -NH2?, a peptide, an alkane group, an alkene group, a polyethyleneglycol group, a saturated fatty acid, an unsaturated fatty acid, a monosaccharide, or a disaccharide; and Z is -COOH or salts or esters thereof, -CONH2?, -NO2?, -PO3? or salts or esters thereof, -C N, or -SO3? or salts or esters thereof, provided that when W is farnesyl, Y is -S-, n = 2, and either T2'? or T2'? is -NHCOCH3?, then Z is not -COOH. The compounds of the invention are capable of interfering with enzymatic methylation of a peptide having the carboxyl-terminal motif -CAAX wherein C = cysteine, A = aliphatic amino acid, and X = any amino acid.
Inventors:
RANDO ROBERT R (US)
Application Number:
PCT/US1992/003063
Publication Date:
October 29, 1992
Filing Date:
April 14, 1992
Export Citation:
Assignee:
HARVARD COLLEGE (US)
International Classes:
A61K31/685; A61K31/10; A61K31/15; A61K31/16; A61K31/19; A61K31/215; A61K31/275; A61K31/70; A61P35/00; A61P43/00; C07C59/60; C07C317/44; C07C317/50; C07C323/01; C07C323/03; C07C323/50; C07C323/52; C07C323/54; C07C323/59; C07C323/60; C07C323/61; C07C323/63; C07C327/58; C07C381/10; C07C391/00; C07F9/38; C07F9/40; (IPC1-7): C07C57/02; C07C57/18; C07C255/00; C07C303/00; C07C307/00; C07C309/00; C07C311/00; C07C315/00; C07C317/00; C07C321/00; C07C323/00; C07C381/00
Other References:
Cell, Volume 57, pages 1167-1177, 30 June 1989, HANDCOCK et al., "All Ras Proteins are Polyiso-prenylated but only some are Palmitoylated" (see entire document).
Proceed Natl. Acad. Sci., Volume 87, 7673-7677, October 1990, LAI et al., "The 8 Submit of Transducin is Farnesylated" (see entire document).
The EMBO Journal, Vol. 3, No. 11, pp. 2581-2585, 1984, WILLAMSEN et al., "Harvey Murine Sarcoma Virus P.21 Ras Protein" (see entire document).
The EMBO Journal, Vol. 8, No. 4, pg. 1093-1098, 1989, GUTIERREZ et al., "Post Translational Processing of P. 21 Ras is Two-Step and Involves Carboxyl-Methylation and Carboxyterminal Proteolysis" (see entire document).
See also references of EP 0580786A4
Proceed Natl. Acad. Sci., Volume 87, 7673-7677, October 1990, LAI et al., "The 8 Submit of Transducin is Farnesylated" (see entire document).
The EMBO Journal, Vol. 3, No. 11, pp. 2581-2585, 1984, WILLAMSEN et al., "Harvey Murine Sarcoma Virus P.21 Ras Protein" (see entire document).
The EMBO Journal, Vol. 8, No. 4, pg. 1093-1098, 1989, GUTIERREZ et al., "Post Translational Processing of P. 21 Ras is Two-Step and Involves Carboxyl-Methylation and Carboxyterminal Proteolysis" (see entire document).
See also references of EP 0580786A4
Download PDF: