Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease
Patent
1993-02-16
1999-11-02
Low, Christopher S. F.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Transferase other than ribonuclease
435 691, 4353201, 4351723, 4352523, 43525233, 435325, 435363, 435366, 435 911, 536 231, 536 232, 930240, 935 14, 935 22, 935 29, 935 32, 935 70, 935 71, 935 72, 935 73, C12N 910
Patent
active
059768517
ABSTRACT:
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.
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Brown Michael S.
Goldstein Joseph L.
Reiss Yuval
Board of Regents , The University of Texas System
Low Christopher S. F.
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