Alpha-conotoxin peptides
The invention relates to relatively short peptides (termed α-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.
1. An isolated α-conotoxin peptide having the generic formula III: Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -Cys-Cys-Xaa 6 -Xaa 7 -Xaa 8 -Xaa 9 -Cys-Xaa 10 -Xaa 11 -Xaa 12 -Xaa 13 -Xaa 14 -Xaa 15 -Xaa 16 -Cys-Xaa 17 -Xaa 18 -Xaa 19 -Xaa 20 -Xaa 21 -Xaa 22 -Xaa 23 -Xaa 24 (SEQ ID NO:3), wherein Xaa 1 is des-Xaa 1 , Xaa 2 is des-Xaa 2 , Xaa 3 is des-Xaa 3 , Xaa 4 is Asp, Xaa 5 is Glu or Gla, Xaa 6 is Ser, Xaa 7 is Asn, Xaa 8 is Pro or hydroxy-Pro, Xaa 9 is Ala, Xaa 10 is Arg, Xaa 11 is Leu, Xaa 12 is Asn, Xaa 13 is Asn, Xaa 14 is Pro or hydroxy-Pro, Xaa 15 is His, Xaa 16 is Ala or Val, Xaa 17 is Arg, Xaa 18 is Arg, Xaa 19 is Arg, Xaa 20 is des-Xaa 20 , Xaa 21 is des-Xaa 21 , Xaa 22 is des-Xaa 22 , Xaa 23 is des-Xaa 23 and Xaa 24 is des-Xaa 24 ; wherein the C-terminus contains a hydroxyl group or an amide group; wherein the His residue may be substituted with a halo-His residue; wherein an Arg residue may be substituted with homoarginine; and wherein the Cys residues may be in the D or L configuration or substituted with homocysteine in the D or L configuration.
2. The isolated α-conotoxin peptide of claim 1 , wherein Xaa 5 is Glu.
3. The isolated α-conotoxin peptide of claim 1 , wherein Xaa 8 is Pro and Xaa 14 is Pro.
4. The isolated α-conotoxin peptide of claim 1 , wherein Xaa 5 is Glu, Xaa 8 is Pro and Xaa 14 is Pro.
5. The isolated α-conotoxin peptide of claim 1 , wherein the halo-His is iodo-His.
6. The isolated α-conotoxin peptide of claim 1 , which is modified to contain an O-glycan, an S-glycan or an N-glycan.