Proteolically resistant cyclotides with angiotensin 1-7 like activity

1. A cyclotide comprising:

a) a cyclotide backbone selected from the group consisting of SEQ ID NOs: 2, 4, and 5 and

b) an angiotensin polypeptide consisting of the sequence of SEQ ID NO: 14,

wherein the cyclotide maintains a biological activity of an angiotensin polypeptide.

2. The cyclotide of claim 1 , further comprising a label or purification marker.

3. A composition comprising the cyclotide of claim 1 and a carrier.

4. The composition of claim 3 , wherein the carrier is a pharmaceutically acceptable carrier.

5. The composition of claim 4 , further comprising a therapeutic agent.

6. A plurality of cyclotides of claim 1 .

7. The plurality of claim 6 , wherein the amino acid sequences of the plurality are the same or different from each other.

8. A composition comprising the plurality of claim 7 and a carrier.

9. The composition of claim 8 , wherein the carrier is a pharmaceutically acceptable carrier.

10. The composition of claim 8 , further comprising a therapeutic agent.

11. A cyclotide comprising a sequence selected from the group consisting of SEQ ID NOs: 17, 18, 19, and 20.

12. An isolated polynucleotide encoding the cyclotide of claim 1 .

13. A composition comprising an isolated polynucleotide of claim 12 and a carrier.

14. The composition of claim 13 , wherein the carrier is a pharmaceutically acceptable carrier.

15. A complement of the polynucleotide of claim 12 .

16. An isolated polynucleotide of claim 15 , further comprising a label or a purification marker.

17. A vector comprising the isolated polynucleotide of claim 12 .

18. An isolated host cell comprising the cyclotide of claim 1 .

19. The isolated host cell of claim 18 , wherein the cell is a eukaryotic cell or a prokaryotic cell.

20. An isolated host cell comprising the polynucleotide of claim 12 .

21. The isolated host cell of claim 20 , wherein the isolated host cell is a eukaryotic cell or a prokaryotic cell.

22. The isolated host cell of claim 21 , wherein the cell is a prokaryotic cell.

23. A method for producing a recombinant cyclotide polypeptide comprising growing the isolated host cell of claim 20 under conditions to express the polynucleotide.

24. The method of claim 23 , further comprising purifying the polypeptide.

25. A method for any one of: promoting vasodilation in a tissue, inhibiting the proliferation of a cell or tissue, or inhibiting angiogenesis, comprising contacting the cell or tissue with a cyclotide of claim 1 , wherein the contacting is in vitro or in vivo.

26. The method of claim 25 , wherein the cell or tissue is a mammalian cell or tissue.

27. The method of claim 26 , wherein the mammalian cell or tissue is a human cell or tissue.

28. A method for inhibiting the growth of a tumor cell comprising contacting the tumor cell with a cyclotide of claim 1 , wherein the contacting is in vitro or in vivo.

29. The method of claim 28 , wherein the tumor cell expresses MAS 1 .

30. The method of claim 28 , wherein the tumor cell is a lung cancer tumor cell or a breast cancer tumor cell.

31. The method of claim 28 , wherein the tumor cell is a mammalian cell, optionally a human cell.

32. A method for any one of: promoting vasodilation in a tissue, inhibiting the proliferation of a cell or tissue, treating myocardial infarction or inhibiting angiogenesis, in a subject in need thereof, comprising administering to a subject in need thereof, an effective amount of cyclotide of claim 1 .

33. A method for inhibiting the growth of a tumor in a subject in need thereof, comprising administering to the subject an effective amount of the cyclotide of claim 1 .

34. The method of claim 33 , wherein the tumor expresses MAS 1.

35. The method of claim 34 , wherein the tumor is a lung cancer tumor or breast cancer tumor.

36. The method of claim 33 , wherein the subject is a mammal, optionally a human.