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    • 9. 发明授权
    • Method of inhibiting a farnesyl transferase enzyme
    • 抑制法呢基转移酶的方法
    • US06790633B1
    • 2004-09-14
    • US09665637
    • 2000-09-19
    • Michael S. BrownJoseph L. GoldsteinYuval Reiss
    • Michael S. BrownJoseph L. GoldsteinYuval Reiss
    • C12Q148
    • C07K1/1077A61K38/00C07K5/1013C07K5/1016C07K5/1019C07K5/1024C07K7/02C07K7/06C07K14/82C12N9/1085
    • Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed 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 p21ras. 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.
    • 公开了用于鉴定,表征和抑制法呢基蛋白转移酶的方法和组合物,涉及各种细胞蛋白的法呢基化的酶,包括癌相关的ras蛋白如p21 。 本文公开的一种法呢基蛋白转移酶在凝胶排阻色谱上显示约70,000至约100,000的分子量。 该酶似乎包含一个或两个约50kDa的亚单位。 公开了用于酶的测定和纯化的方法,以及在筛选方案中使用纯化酶鉴定可能的抗癌剂的方法,所述抗癌剂抑制酶,从而阻止蛋白质如p21 的表达。 还公开了作为酶的假底物或纯抑制剂的化合物家族,因此可用于抑制酶。 最有效的抑制剂是其氨基末端是半胱氨酸的四肽的第三位发生苯丙氨酸的抑制剂。
    • 10. 发明授权
    • Methods and compositions for the identification, characterization, and
inhibition of farnesyl protein transferase
    • 用于鉴定,表征和抑制法呢基蛋白转移酶的方法和组合物
    • US5976851A
    • 1999-11-02
    • US21625
    • 1993-02-16
    • Michael S. BrownJoseph L. GoldsteinYuval Reiss
    • Michael S. BrownJoseph L. GoldsteinYuval Reiss
    • C07K5/103C12N9/10
    • C12N9/1085C07K5/1013
    • Disclosed are methods and compositions for the identification, characterization and inhibition of mammalian farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21.sup.ras. The nucleotide and amino acid sequences of the .alpha. and .beta. subunits of both rat and human farnesyl transferase are disclosed, as are methods and compositions for the preparation of farnesyl transferase 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.
    • 公开了用于鉴定,表征和抑制哺乳动物法尼糖蛋白转移酶的方法和组合物,涉及各种细胞蛋白的法呢基化的酶,包括与癌相关的ras蛋白如p21ras。 公开了大鼠和人类法呢基转移酶的α和β亚基的核苷酸和氨基酸序列,以及在其两个亚基的分子克隆和共表达之后,通过重组方法制备法呢基转移酶的方法和组合物, 用于酶的测定和纯化,以及在筛选方案中使用纯化酶鉴定可能的抗癌剂的方法,所述抗癌剂抑制酶,从而阻止诸如p21ras的蛋白质的表达。 还公开了作为酶的假底物或纯抑制剂的化合物家族,因此可用于抑制酶。 最有效的抑制剂是其氨基末端是半胱氨酸的四肽的第三位发生苯丙氨酸的抑制剂。