Polypeptides capable of interacting with human topoisomerase III alpha

Abstract

The invention concerns novel peptides capable of interacting with the human topoisomerase IIIα and the nucleic acid sequences coding for said polypeptides. The invention also concerns a method for identifying compounds capable of interacting with said polypeptides and a method for identifying molecules capable of modulating the interaction of the topoisomerase IIIα with said polypeptides.

1 . Nucleotide sequence encoding a polypeptide capable of interacting with topoisomerase IIIα.  
     
     
         2 . Nucleotide sequence according to  claim 1 , characterized in that it encodes a polypeptide comprising all or part of the polypeptide sequence SEQ ID No. 4 or of its derivatives.  
     
     
         3 . Nucleotide sequence according to either of claims  1  and  2 , characterized in that it comprises all or part of the nucleotide sequence SEQ ID No. 3 or of its derivatives.  
     
     
         4 . Polypeptide, characterized in that it is capable of interacting with topoisomerase IIIα.  
     
     
         5 . Polypeptide according to  claim 4 , characterized in that it comprises all or part of the polypeptide sequence SEQ ID No. 4 or of a sequence derived therefrom.  
     
     
         6 . Polypeptide according to  claim 4 , characterized in that it consists of the polypeptide sequence corresponding to residues 318-662 of the sequence SEQ ID No. 5 or of a sequence derived therefrom.  
     
     
         7 . Use of a polypeptide or of a polypeptide fragment according to  claims 4  to  6 , for slowing down, inhibiting, stimulating or modulating the activity of topoisomerase IIIα.  
     
     
         8 . Antibody or antibody fragment directed against a polypeptide according to one of  claims 4  to  6 .  
     
     
         9 . Method for detecting or identifying compounds capable of binding to a polypeptide as defined according to one of  claims 4  to  6 , characterized in that the following steps are carried out: 
 a—a molecule or a mixture containing various molecules, optionally unidentified, is brought into contact with a polypeptide as defined according to one of  claims 4  to  6  under conditions allowing the interaction between said polypeptide and said molecule in the case where the latter might possess affinity for said polypeptide, and,  
 b—the molecules bound to said polypeptide are detected and/or isolated.  
 
     
     
         10 . Method for detecting or identifying compounds capable of modulating or inhibiting the interaction between topoisomerase III-α and a polypeptide as defined according to  claims 4  to  6 , characterized in that the following steps are carried out: 
 a—the binding of topoisomerase IIIα or of a fragment thereof to said polypeptide is carried out;  
 b—a compound to be tested for its capacity to inhibit the binding between topoisomerase IIIα and said polypeptide is added;  
 c—the displacement or inhibition of the binding of topoisomerase IIIα to said polypeptide is determined;  
 d—the compounds which prevent or which impede the binding between topoisomerase IlIα and said polypeptide are detected and/or isolated.  
 
     
     
         11 . Ligand for a polypeptide as defined according to  claims 4  to  6 , capable of being obtained according to the method of  claim 9 .  
     
     
         12 . Ligand capable of modulating or inhibiting the interaction between topoisomerase IIIα and a polypeptide as defined according to  claims 4  to  6 , capable of being obtained according to the method of  claim 10 .  
     
     
         13 . Use of a ligand according to  claim 11  or  12  for the preparation of a medicament intended for the prevention, improvement or treatment of diseases involving a cell cycle dysfunction.  
     
     
         14 . Pharmaceutical composition comprising, as active ingredient, at least ligand according to either of claims  11  and  12  or an antibody according to  claim 8 .  
     
     
         15 . Composition according to  claim 14 , intended for modulating slowing down or inhibiting the activity of topoisomerase IIIα.  
     
     
         16 . Composition according to either of claims  14  and  15 , intended for the prevention, improvement or treatment of diseases involving a cell cycle dysfunction.