Peptides that enhance acetylcholinesterase expression
The present invention provides novel chimeric peptides and novel methods for treating animals including humans by administering the novel chimeric peptides. In particular, the invention is useful for enhancing endogenous acetylcholinesterase expression in individuals exposed to organophosphate compounds, such as nerve gases and pesticides.
1. A chimeric polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.
2. The chimeric polypeptide according to claim 1 , wherein the polypeptide is derived from acetylcholinesterase collagenic tail peptide.
3. The chimeric polypeptide according to claim 1 , wherein the polypeptide has an amino acid sequence comprising SEQ ID NO:2.
4. The chimeric polypeptide according to claim 1 , further comprising an endoplasmic retention signal.
5. The chimeric polypeptide according to claim 4 , wherein the endoplasmic retention signal has an amino acid sequence comprising SEQ ID NO:3.
6. The chimeric polypeptide according to claim 1 , further comprising a signal for conjugating a label, wherein the label is fluorescent.
7. A pharmaceutical composition comprising a chimeric polypeptide and a pharmaceutically acceptable carrier, excipient, or diluent, wherein the chimeric polypeptide enhances endogenous acetylcholinesterase expression, the chimeric polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.
8. A method of treating an animal exposed to an organophosphate comprising administering to the animal a therapeutically effective amount of a chimeric polypeptide, wherein the chimeric polypeptide enhances, endogenous acetylcholinesterase expression, the chimeric polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.
9. The method of claim 8 , wherein the therapeutically effective amount of the chimeric polypeptide is administered parenterally, intramuscularly, intraperitoneally, subcutaneously, or intravenously.
10. The method of claim 8 , wherein the therapeutically effective amount of the chimeric polypeptide is administered in a dose range from about 0.1 mg/kg to about 10 mg/kg of body weight per day.
11. A method of treating an animal exposed to an organophosphate comprising administering to the animal a therapeutically effective amount of a pharmaceutical composition comprising a chimeric polypeptide wherein the chimeric polypeptide enhances endogenous acetylcholinesterase expression, the chimeric polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.
12. The method of claim 11 , wherein the therapeutically effective amount of the pharmaceutical composition is administered parenterally, intramuscularly, intraperitoneally, subcutaneously, or intravenously.
13. The method of claim 11 , wherein the therapeutically effective amount of the pharmaceutical composition is administered in a dose range from about 0.1 mg/kg to about 10 mg/kg of body weight per day.
14. The method of claim 10 or 11 , wherein the organophosphate is a nerve gas.
15. The method of claim 14 , wherein the nerve gas is selected from the group consisting of sarin, soman, tabun and vx.
16. The method of claim 8 or 11 , wherein the organophosphate is a pesticide.
17. The method of claim 16 , wherein the pesticide is selected from the group consisting of malathion, parathion, diazinon, fenthion, dichlorvos, and chlorpyrifos.
18. A method of enhancing endogenous acetylcholinesterase expression in an animal in need thereof, comprising administering to the animal a therapeutically effective amount of a chimeric polypeptide wherein the chimeric polypeptide enhances endogenous acetylcholinesterase expression, the chimeric polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEC) ID NO: 11.
19. The method of claim 18 , wherein the therapeutically effective amount of the chimeric polypeptide is administered parenterally, intramuscularly, intraperitoneally, subcutaneously, or intravenously.
20. The method of claim 18 , wherein the therapeutically effective amount of the chimeric polypeptide is administered in a dose range from about 0.1 mg/kg to about 10 mg/kg of body weight per day.
21. A method of enhancing endogenous acetylcholinesterase expression in an animal in need thereof, comprising administering to the animal a therapeutically effective amount of a pharmaceutical composition comprising a chimeric polypeptide wherein the chimeric polypeptide enhances endogenous acetylcholinesterase expression, the chimeric polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.
22. The method of claim 21 , wherein the therapeutically effective amount of the pharmaceutical composition is administered parenterally, intramuscularly, intraperitoneally, subcutaneously, or intravenously.
23. The method of claim 21 , wherein the therapeutically effective amount of the pharmaceutical composition is administered in a dose range from about 0.1 mg/kg to about 10 mg/kg of body weight per day.
24. A kit for treating organophosphate poisoning comprising a therapeutically effective amount of a chimeric polypeptide according to claim 1 .