申请人:The President and Fellows of Harvard College
公开号:US05202456A1
公开(公告)日:1993-04-13
The invention features a compound of the formula W-Y-Q-Z or W-Y-Z wherein W is a farnesyl group, a geranylgeranyl group, a substituted farnesyl group or a substituted geranylgeranyl group; ##STR1## wherein n=1, 2, 3, 4, 5, or 6; each of T.sub.1' . . . T.sub.n' and T.sub.1" . . . T.sub.n" is independently: Fl, Br, --NHCOCH.sub.3, --NH.sub.2, a peptide, an alkane group, an alkene group, an polyethyleneglycol group, a saturated fatty acid, an unsaturated fatty acid, a monosaccharide, or a disaccharide; and Z is --COOH or salts or esters thereof, --CONH.sub.2, --NO.sub.2, --PO.sub.3 or salts or esters thereof, --C N, or --SO.sub.3 or salts or esters thereof, provided that when W is farnesyl, Y is --S--, n=2, and either T.sub.2' or T.sub.2" is --NHCOCH.sub.3, 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.
该发明涉及一个具有公式W-Y-Q-Z或W-Y-Z的化合物,其中W是一种法尼基基团、一种戈莱基基团、一种取代的法尼基基团或一种取代的戈莱基基团;其中n=1、2、3、4、5或6;每个T.sub.1' . . . T.sub.n'和T.sub.1" . . . T.sub.n"独立地为:Fl、Br、--NHCOCH.sub.3、--NH.sub.2、一个肽、一个烷基基团、一个
烯基基团、一个聚
乙二醇基团、一个饱和
脂肪酸、一个不饱和
脂肪酸、一个
单糖或一个二糖;Z为--COOH或其盐或
酯、--CONH.sub.2、--NO.sub.2、--PO.sub.3或其盐或
酯、--CN或--SO.sub.3或其盐或
酯,但当W为法尼基、Y为--S--、n=2且T.sub.2'或T.sub.2"为--NHCOCH.sub.3时,Z不是--COOH。该发明的化合物能够干扰具有羧基末端基序列--
CAAX的肽的酶
甲基化。