Ghrelin binding nucleic acids

Abstract

The present invention is related to a nucleic acid antagonist of ghrelin.

1 . An antagonist of ghrelin, wherein the antagonist is a nucleic acid which specifically binds ghrelin. 
     
     
         2 . An antagonist of the GHSR 1a receptor system, wherein the antagonist is the nucleic acid of  claim 1 . 
     
     
         3 . The antagonist according to  claim 1 , wherein said nucleic acid comprises at least one L-nucleotide. 
     
     
         4 . The antagonist of  claim 3 , wherein the antagonist is an L-nucleic acid. 
     
     
         5 . The antagonist of  claim 1 , wherein said ghrelin is L-ghrelin. 
     
     
         6 . The antagonist of  claim 1 , wherein said nucleic acid comprises any one of SEQ ID NO:7 to SEQ ID NO:125. 
     
     
         7 . The antagonist of  claim 1 , wherein the nucleic acid is selected from the group consisting of DNA, RNA and combinations thereof. 
     
     
         8 . The antagonist of  claim 1 , wherein said nucleic acid has a Kd less than 1 μM. 
     
     
         9 . The antagonist of  claim 8 , wherein said nucleic acid has a Kd less than 0.25 μM. 
     
     
         10 . The antagonist of  claim 9 , wherein said nucleic acid has a Kd less than 0.1 μM. 
     
     
         11 . The antagonist of  claim 10 , wherein said nucleic acid has a Kd less than 0.01 μM. 
     
     
         12 . The antagonist of  claim 1 , wherein said nucleic acid has a Kd more than 100 nM. 
     
     
         13 . The antagonist of  claim 12 , wherein said nucleic acid has a Kd more than 10 nM. 
     
     
         14 . The antagonist of  claim 13 , wherein said nucleic acid has a Kd more than 1 nM. 
     
     
         15 . The antagonist of  claim 1 , wherein said nucleic acid has a Kd more than 0.05 nM. 
     
     
         16 . The antagonist of  claim 1 , wherein the nucleic acid comprises 15 to 150 nucleotides. 
     
     
         17 . The antagonist of  claim 16 , wherein the nucleic acid comprises 20 to 60 nucleotides. 
     
     
         18 . The antagonist of  claim 17 , wherein said nucleic acid comprises 30 to 50 nucleotides. 
     
     
         19 . A method for making the nucleic acid of  claim 1 , comprising the following steps:
 a) generating a heterogeneous population of nucleic acids;   b) contacting the population of step a) with a ghrelin;   c) separating the nucleic acid(s) not interacting with said ghrelin;   d) optionally separating the nucleic acid(s) interacting with said ghrelin; and   e) optionally sequencing the nucleic acid(s) interacting with said ghrelin.   
     
     
         20 . The method according to  claim 19 , further comprising subsequent to step c), step ca) amplifying nucleic acid(s) interacting with ghrelin. 
     
     
         21 . The method according to  claim 19 , wherein steps b) to d) are repeated. 
     
     
         22 . A method for making the L-nucleic acid of  claim 4  comprising:
 a) generating a heterogeneous population of D-nucleic acids; 
 b) contacting the population of step a) with a D-ghrelin; 
 c) separating the D-nucleic acid not interacting with said D-ghrelin; 
 d) sequencing the D-nucleic acid interacting with said D-ghrelin; and 
 e) synthesising the L-nucleic acid sequence(s) which is/are identical to the sequence of the D-nucleic acid(s) obtained in step d). 
 
     
     
         23 . The method according to  claim 22 , further comprising subsequent to step c):
 ca) amplifying the D-nucleic acid interacting with D-ghrelin.   
     
     
         24 . The method according to  claim 22 , characterised in that steps b) to e) are repeated. 
     
     
         25 . The antagonist of  claim 1 , further comprising a pharmaceutically acceptable carrier. 
     
     
         26 . A complex comprising ghrelin and the antagonist of  claim 1 . 
     
     
         27 . The complex  claim 26 , which is crystalline. 
     
     
         28 . A method for identifying a ghrelin comprising exposing a sample suspected of containing a ghrelin to the antagonist of  claim 1  and detecting complexes of said ghrelin and said antagonist. 
     
     
         29 . A method for screening for the antagonist of  claim 1  comprising:
 providing a candidate ghrelin antagonist, 
 providing the antagonist of  claim 1 , 
 providing a test system providing a signal in the presence of a ghrelin antagonist, and 
 determining whether the candidate ghrelin antagonist is a ghrelin antagonist.