Novel compounds

Abstract

h-TREK1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing h-TREK1 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

What is claimed is:  
     
         1 . An isolated polypeptide selected from the group consisting of: 
 (i) an isolated polypeptide comprising an amino acid sequence selected from the group having at least: 
 (a) 97% identity;  
 (b) 98% identity; or  
 (c) 99% identity;  
 to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2;  
   (ii) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:2;    (iii) an isolated polypeptide which is the amino acid sequence of SEQ ID NO:2;    (iv) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:6 or    (v) an isolated polypeptide which is the amino acid sequence of SEQ ID NO:6.    
     
     
         2 . An isolated polynucleotide selected from the group consisting of: 
 (i) an isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide that has at least 
 (a) 97% identity;  
 (b) 98% identity; or  
 (c) 99% identity;  
   to the amino acid sequence of SEQ ID NO:2, over the entire length of SEQ ID NO:2;    (ii) an isolated polynucleotide comprising a nucleotide sequence that has at least: 
 (a) 90% identity; or  
 (b) 95% identity;  
   over its entire length to a nucleotide sequence encoding the polypeptide of SEQ ID NO:2;    (iii) an isolated polynucleotide comprising a nucleotide sequence which has at least: 
 (a) 90% identity; or  
 (b) 95% identity;  
   to that of SEQ ID NO:1 over the entire length of SEQ ID NO:1;    (iv) an isolated polynucleotide comprising a nucleotide sequence encoding the polypeptide of SEQ ID NO:2;    (v) an isolated polynucleotide which is the polynucleotide of SEQ ID NO:1; or    (vi) an isolated polynucleotide obtainable by screening an appropriate library under stringent hybridization conditions with a labelled probe having the sequence of SEQ ID NO:1or a fragment thereof.;    (vii) an isolated polynucleotide comprising a nucleotide sequence that has at least: 95% identity over its entire length to a nucleotide sequence encoding the polypeptide of SEQ ID NO:6;    (viii) an isolated polynucleotide comprising a nucleotide sequence which has at least: 95% identity to that of SEQ ID NO:5 over the entire length of SEQ ID NO:5;    (ix) an isolated polynucleotide comprising a nucleotide sequence encoding the polypeptide of SEQ ID NO:6;    (x) an isolated polynucleotide which is the polynucleotide of SEQ ID NO:5; or    (xi) an isolated polynucleotide obtainable by screening an appropriate library under stringent hybridization conditions with a labelled probe having the sequence of SEQ ID NO:5 or a fragment thereof.;    or a nucleotide sequence complementary to said isolated polynucleotide.    
     
     
         3 . An antibody immunospecific for the polypeptide of  claim 1 .  
     
     
         4 . A method for the treatment of a subject: 
 (i) in need of enhanced activity or expression of the polypeptide of  claim 1  comprising: 
 (a) administering to the subject a therapeutically effective amount of an agonist to said polypeptide; and/or  
 (b) providing to the subject an isolated polynucleotide comprising a nucleotide sequence encoding said polypeptide in a form so as to effect production of said polypeptide activity in vivo.; or  
   (ii) having need to inhibit activity or expression of the polypeptide of  claim 1  comprising: 
 (a) administering to the subject a therapeutically effective amount of an antagonist to said polypeptide; and/or  
 (b) administering to the subject a nucleic acid molecule that inhibits the expression of a nucleotide sequence encoding said polypeptide; and/or  
 (c) administering to the subject a therapeutically effective amount of a polypeptide that competes with said polypeptide for its ligand, substrate, or receptor.  
   
     
     
         5 . A process for diagnosing a disease or a susceptibility to a disease in a subject related to expression or activity of the polypeptide of  claim 1  in a subject comprising: 
 (a) determining the presence or absence of a mutation in the nucleotide sequence encoding said polypeptide in the genome of said subject; and/or  
 (b) analyzing for the presence or amount of said polypeptide expression in a sample derived from said subject.  
 
     
     
         6 . A method for screening to identify compounds which stimulate or which inhibit the function of the polypeptide of  claim 1  which comprises a method selected from the group consisting of: 
 (a) measuring the binding of a candidate compound to the polypeptide (or to the cells or membranes bearing the polypeptide) or a fusion protein thereof by means of a label directly or indirectly associated with the candidate compound;  
 (b) measuring the binding of a candidate compound to the polypeptide (or to the cells or membranes bearing the polypeptide) or a fusion protein thereof in the presense of a labeled competitor;  
 (c) testing whether the candidate compound results in a signal generated by activation or inhibition of the polypeptide, using detection systems appropriate to the cells or cell membranes bearing the polypeptide;  
 (d) mixing a candidate compound with a solution containing a polypeptide of  claim 1 , to form a mixture, measuring activity of the polypeptide in the mixture, and comparing the activity of the mixture to a standard; or  
 (e) detecting the effect of a candidate compound on the production of mRNA encoding said polypeptide and said polypeptide in cells, using for instance, an ELISA assay.  
 
     
     
         7 . An agonist or an antagonist of the polypeptide of  claim 1 .  
     
     
         8 . An expression system comprising a polynucleotide capable of producing a polypeptide of  claim 1  when said expression system is present in a compatible host cell.  
     
     
         9 . A process for producing a recombinant host cell comprising transforming or transfecting a cell with the expression system of  claim 8  such that the host cell, under appropriate culture conditions, produces a polypeptide selected from the group consisting of: 
 (i) a polypeptide comprising an amino acid sequence having at least 97% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2; or  
 (ii) a polypeptide comprising an amino acid sequence having the sequence of SEQ ID NO:6.  
 
     
     
         10 . A recombinant host cell produced by the process of  claim 9 .  
     
     
         11 . A membrane of a recombinant host cell of  claim 10  expressing a polypeptide selected from the group consisting of: 
 (i) a polypeptide comprising an amino acid sequence having at least 97% identity to the amino acid sequence of SEQ ID NO:2 over the entire length of SEQ ID NO:2; or (ii) a polypeptide comprising an amino acid sequence having the sequence of SEQ ID NO:6.  
 
     
     
         12 . A process for producing a polypeptide comprising culturing a host cell of  claim 10  under conditions sufficient for the production of said polypeptide and recovering the polypeptide from the culture.  
     
     
         13 . An isolated polynucleotide selected form the group consisting of 
 (a) an isolated polynucleotide comprising a nucleotide sequence which has at least 90%, 95%, 97% identity to SEQ ID NO:3 over the entire length of SEQ ID NO:3;    (b) an isolated polynucleotide comprising the polynucleotide of SEQ ID NO:3;    (c) the polynucleotide of SEQ ID NO:3; or    (d) an isolated polynucleotide comprising a nucleotide sequence encoding a polypeptide which has at least 99% identity to the amino acid sequence of SEQ ID NO:4, over the entire length of SEQ ID NO:4.    
     
     
         14 . A polypeptide selected from the group consisting of: 
 (a) a polypeptide which comprises an amino acid sequence which has at least 99% identity to that of SEQ ID NO:4 over the entire length of SEQ ID NO:4;    (b) a polypeptide which has an amino acid sequence which is at least 99% identity to the amino acid sequence of SEQ ID NO:4 over the entire length of SEQ ID NO:4;    (c) a polypeptide which comprises the amino acid of SEQ ID NO:4;    (d) a polypeptide which is the polypeptide of SEQ ID NO:4; or    (e) a polypeptide which is encoded by a polynucleotide comprising the sequence contained in SEQ ID NO:3.