Therapeutic peptides and use thereof against huntington's disease
Fusion proteins that contain the fusion of (i) a peptide of less than 100 amino acids comprising a first amino acid sequence comprising AASSG (SEQ ID NO: 1) and a second amino acid sequence comprising XAGXDXXTEXPXS (SEQ ID NO: 2), wherein X designates any amino acid, and (ii) a protein transduction domain (PTD) are provided, along with pharmaceutical compositions containing the fusion protein. The proteins can be used to treat Huntington's disease.
1. A fusion protein, comprising:
(i) a peptide of less than 100 amino acids comprising:
a first amino acid sequence comprising AASSG (SEQ ID NO: 1), and
a second amino acid sequence comprising XAGXDXXTEXPXS (SEQ ID NO: 2), wherein X designates any amino acid; and
(ii) a protein transduction domain (PTD).
2. The fusion protein according to claim 1 , wherein the second amino acid sequence is SAGHDIITEQPRS (SEQ ID NO: 3) or NAGEDAPTEAPSS (SEQ ID NO: 6).
3. The fusion protein according to claim 1 , wherein said peptide comprises SEQ ID NO: 4 or SEQ ID NO: 5.
4. The fusion protein according to claim 1 , wherein the protein transduction domain is Transacting Activator of Transcription (TAT) peptide or Penetratin peptide.
5. The fusion protein according to claim 4 , wherein the protein transduction domain comprises SEQ ID NO: 11.
6. The fusion protein according to claim 4 , wherein the protein transduction domain comprises SEQ ID NO: 12.
7. The fusion protein according to claim 4 , wherein the fusion protein consists of the amino acid sequence SEQ ID NO: 13.
8. A polynucleotide coding for the fusion protein according to claim 1 .
9. An expression vector containing the polynucleotide according to claim 8 .
10. The vector according to claim 9 , the vector being a virus type expression vector.
11. A host cell containing the expression vector according to claim 9 .
12. A pharmaceutical composition comprising
a fusion protein comprising:
(i) a peptide of less than 200 amino acids comprising:
a first amino acid sequence comprising AASSG (SEQ ID NO: 1), and
a second amino acid sequence comprising XAGXDXXTEXPXS (SEQ ID NO: 2), wherein X designates any amino acid, and
(ii) a protein transduction domain (PTD), or
a polynucleotide coding for said fusion protein, or
an expression vector containing said polynucleotide, in association with a pharmaceutically acceptable carrier.
13. The pharmaceutical composition according to claim 12 , wherein said peptide comprises SEQ ID NO: 4 or SEQ ID NO: 5.
14. The pharmaceutical composition according to claim 12 , wherein the second amino acid sequence consists of the sequence selected from the group consisting of SAGHDIITEQPRS (SEQ ID NO: 3) and NAGEDAPTEAPSS (SEQ ID NO: 6).
15. The pharmaceutical composition according to claim 12 , wherein the fusion protein consists of the amino acid sequence SEQ ID NO: 13.
16. The pharmaceutical composition according to claim 12 , wherein the protein transduction domain is selected from the group consisting of Transacting Activator of Transcription (TAT) peptide and Penetratin peptide.
17. The pharmaceutical composition according to claim 16 , wherein the TAT peptide consists of the amino acid sequence SEQ ID NO: 11.
18. The pharmaceutical composition according to claim 16 , wherein the Penetratin peptide consists of the amino acid sequence SEQ ID NO: 12.
19. A method for treating Huntington's disease in a patient in need thereof, said method comprising administering to the patient an effective amount of
an isolated peptide of less than 200 amino acids comprising:
a first amino acid sequence AASSG (SEQ ID NO: 1), and
a second sequence XAGXDXXTEXPXS (SEQ ID NO: 2), wherein X designates any amino acid,
or
a fusion protein comprising
(i) a peptide of less than 200 amino acids comprising:
a first amino acid sequence AASSG (SEQ ID NO: 1), and
a second amino acid sequence XAGXDXXTEXPXS (SEQ ID NO: 2), wherein X designates any amino acid, and
(ii) a protein transduction domain (PTD), or
a polynucleotide coding for said isolated peptide or said fusion protein, or
an expression vector containing said polynucleotide.
20. The method for treating Huntington's disease according to claim 19 , wherein said isolated peptide comprises SEQ ID NO: 4 or SEQ ID NO: 5.
21. The method for treating Huntington's disease according to claim 19 , wherein the fusion protein consists of the amino acid sequence SEQ ID NO: 13.