Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.

Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.

Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.

Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. ?-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.

Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.

Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. ?-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.

Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. &agr;-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.

Abstract: Prenylating enzymes are involved in modifying oncoproteins, such as RAS, so that growth of neoplastic cells becomes uncontrolled. Inactivation of such enzymes can prevent uncontrolled growth. &agr;-Dicarbonyl compounds can be used to covalently modify and thereby inactivate prenylating enzymes such as protein farnesyltransferase and protein geranylgeranyltransferase. The compounds can be designed to enhance affinity and/or specificity for a particular protein substrate.

Abstract: Oncoproteins such as Ras and RhoB are known to induce cell division in an unrestrained manner when such proteins are localized at the inner surface of a cancer cell membrane. The localization is effected by the prenylation reaction, whereby a hydrophobic group (e.g. a farnesyl group) is attached to the protein in the presence of an enzyme (e.g. farnesyl protein transferase). Deactivation of the prenylation enzyme through covalent modification can therefore ultimately result in the mitigation and/or cessation of cancer cell growth. Various prenylation inhibitors having the necessary structural groups to bond covalently, or essentially irreversibly, to the prenylation enzyme include carbonyl or thiocarbonyl compounds (or masked versions of these compounds) and alpha oxo-epoxides bonded to a hydrophobic, substrate-mimicking group. The carbonyl or thiocarbonyl compounds also contain a nucleofugal atom or group to enhance the tendency to form covalent bonds.