Recombinant thrombin receptor and related pharmaceuticals
AssigneeCOR Therapeutics, Inc.
InventorsShaun R. Coughlin, Robert M. Scarborough
Life of this patent
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Abstract
The DNA encoding the cell surface receptor for thrombin has been cloned and sequenced. The availability of this DNA permits the recombinant production of thrombin receptor which can be produced at cell surfaces and is useful in assay systems both for the detection of thrombin and for the evaluation of candidate thrombin agonists and antagonists. Further, the elucidation of the structure of the thrombin receptor permits the design of agonist and antagonist compounds which are useful diagnostically and therapeutically. The availability of the thrombin receptor also permits production of antibodies specifically immunoreactive with the receptor per se or with specific regions thereof which are also useful diagnostically or therapeutically.
Claims9
A peptide capable of activating thrombin receptor, which peptide is of the formula
- AA.sub.x --AA.sub.y --(AA.sub.i).sub.n --Z (1)
- wherein AA.sub.x is a small amino acid or threonine, and A.sub.y is a neutral/nonpolar/aromatic amino acid residue or is a neutral/nonpolar/large/nonaromatic amino acid containing a cyclic portion;
- wherein AA represents an amino acid residue and the subscript i is an integer which denotes the position of said amino acid residue downstream (N.fwdarw.C) of the AA.sub.y residue of formula (1), and n is an integer of 2-12 so that (AA.sub.i).sub.n represents AA.sub.1 -AA.sub.2 ;
- AA.sub.1 -AA.sub.2 -AA.sub.3 ;
- AA.sub.1 -AA.sub.2 -AA.sub.3 -AA.sub.4 ;
- through AA.sub.1 -AA.sub.2 -AA.sub.3 -AA.sub.4 -AA.sub.5 -AA.sub.6 -AA.sub.7 -AA.sub.8 -AA.sub.9 -AA.sub.10 -AA.sub.11 -AA.sub.12 ;
- with the proviso that if n=2, Z must be of the formula NR'R' wherein at least one R' is alkyl (1-6C) containing at least one polar substituent;
- AA.sub.1 is a neutral or basic amino acid having a free .alpha.-amino group in the L-configuration;
- AA.sub.2 is a neutral or basic amino acid residue in the L-configuration;
- AA.sub.4 -AA.sub.12 are L-amino acid residues;
- and
- Z is a substituent that does not prevent said activating with the proviso that said peptide is not a peptide selected from the group consisting of SFLLKNPNDKYEPF;
- SFLLRNPNDKYEP;
- SFLLRNPNDKYE;
- SFLLRNPNDKY;
- SFLLRNPNDK;
- SFLLRNPND;
- SFLLRNPN;
- SFLLRNP;
- SFLLRN;
- SFLLR;
- SFLL;
- and SFL, and the amidated forms thereof.
Dependencies are inferred from the claim text.