α-conotoxin MII analogs
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:
(a) Gly-Cys-Cys-Ser-Asn-Pro-Val-Cys-Ala-Leu-Glu-His-Ser-Asn-Ala-Cys (SEQ ID NO: 13);
(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; one or both of the Asn residues is or are substituted with N-glycosylated Asn; the Cys residues are in D or L configuration; or one or more of the Cys residues is or are substituted with homocysteine in the D or L configuration; and
(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:13.
4. The pharmaceutical composition of claim 2 , wherein the conopeptide is the peptide of SEQ ID NO:13.