Alpha-conotoxin mii analogs

Abstract

The invention relates to novel conopeptides and/or novel uses of conopeptides. The conopeptides of the invention are analogs of α-Conotoxin MII that are selective for α6-containing nAChRs as described herein.

1 . An isolated conopeptide selected from the group consisting of: 
       
         
           
                 
               
                   (SEQ ID NO: 15) 
                 
                   (a) Gly-Cys-Cys-Ser-Asn-Pro-Val-Cys-His-Leu-Ala- 
                 
                     
                 
                   His-Ser-Asn-Ala-Cys; 
                 
             
                
                
                
                
               
            
           
         
         (b) a derivative of (a) having α6-containing nicotinic acetylcholine receptor binding activity, wherein the derivative is a peptide in which the Pro residue is substituted with hydroxy-Pro or O-glycosylated hydroxy-Pro; one or both of the Ser residues is or are substituted with O-glycosylated Ser, Thr, O-glycosylated Thr or a synthetic hydroxylated amino acid; one or both of the Asn residues is or are substituted with N-glycosylated Asn; the Cys residues are in D or L configuration; one or more of the Cys residues is or are substituted with homocysteine in the D or L configuration; one or more pairs of Cys residues is or are replaced pairwise with a Ser/(Glu or Asp) combination or a Lys/(Glu or Asp) combination, wherein the synthetic hydroxylated amino acid is selected from the group consisting of 4-hydroxymethyl-Phe 4-hydroxyphenyl-Gly, 2,6-dimethyl-Tyr and 5-amino-Tyr; 
         (c) a physiologically acceptable salt of (a) or (b). 
       
     
     
         2 . A pharmaceutical composition comprising the conopeptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         3 . The isolated conopeptide of  claim 1 , wherein the conopeptide is the peptide of SEQ ID NO:15. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the conopeptide is the peptide of SEQ ID NO:15.