Claims
- 1. An isolated and purified peptide comprising: a biologically active portion of Dendroaspis natriuretic peptide, or a variant thereof.
- 2. The peptide of claim 1 wherein the peptide has at least one activity selected from the group consisting of vasodilation, natriuresis, diuresis and renin-suppressing activity.
- 3. The peptide of claim 1 further comprising at least a portion of a natriuretic peptide that is not Dendroaspis natriuretic peptide.
- 4. The peptide of claim 3 wherein the portion of the peptide comprising Dendroaspis natriuretic peptide is at the carboxy-terminus of the peptide.
- 5. The peptide of claim 3 wherein the natriuretic peptide that is not Dendroaspis natriuretic peptide is brain natriuretic peptide.
- 6. The peptide of claim 3 wherein the natriuretic peptide that is not Dendroaspis natriuretic peptide is C-type natriuretic peptide.
- 7. The peptide of claim I comprising SEQ ID NO:3.
- 8. The peptide of claim 3 comprising SEQ ID NO:11.
- 9. The peptide of claim 3 comprising SEQ ID NO:2.
- 10. A method to inhibit or prevent heart failure in a mammal, comprising:
administering to the mammal an effective amount of the peptide of claim 1 in a pharmacuetically acceptable delivery vehicle.
- 11. The method of claim 10 wherein the peptide is administered parenterally.
- 12. The method of claim 10 wherein the peptide comprises SEQ ID NO: 1.
- 13. The method of claim 10 wherein the peptide comprises SEQ ID NO:2.
- 14. The method of claim 10 wherein the peptide comprises SEQ ID NO:3.
- 15. The method of claim 10 wherein the administration is local.
- 16. The method of claim 10 wherein the administration is systemic.
- 17. A peptide compound of the formula (H)-Pro-Ser-Leu-Arg-Asp-Pro-Arg-Pro-Asn-Ala-Pro-Ser-Thr-Ser-Ala-(R) (SEQ ID NO:3), wherein R is OH, NH2, NHR3 or N(R3)(R4), wherein R3 and R4 are independently phenyl or (C1-C4)alkyl; or a pharmaceutically acceptable salt thereof.
- 18. A peptide compound of the formula (H)-Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-Pro-Ser-Leu-Arg-Asp-Pro-Arg-Pro-Asn-Ala-Pro-Ser-Thr-Ser-Ala-(R) (SEQ ID NO:1), wherein R is OH, NH2, NHR3 or N(R3)(R4), wherein R3 and R4 are independently phenyl or (C1-C4)alkyl; wherein the two Cys residues are connected by a disulfide bond; or a pharmaceutically acceptable salt thereof.
- 19. A peptide compound of the formula: (H)-Gly-Leu-Ser-Lys-Gly-Cys-Phe-Gly-Leu-Lys-Asp-Arg-Ile-Gly-Ser-Met-Ser-Gly-Leu-Gly-Cys-Pro-Ser-Leu-Arg-Asp-Pro-Arg-Pro-Asn-Ala-Pro-Ser-Thr-Ser-Ala-(R), wherein R is OH, NH2, NHR3 or N(R3)(R4), wherein R3 and R4 are independently phenyl or (C1-C4)alkyl; wherein the two Cys residues are connected by a disulfide bond; or a pharmaceutically acceptable salt thereof.
- 20. A composition useful as a natriuretic, diuretic, renin-suppressor, or vasodilator, comprising of: a therapeutically effective amount of the compound of claim 17, 18, 19, or a combination thereof, with a pharmaceutically acceptable carrier.
- 21. A method to treat heart failure in a mammal, comprising: administering to the mammal an effective amount of Dendroaspis natriuretic peptide, a biologically active variant or portion thereof in a pharmaceutically acceptable delivery vehicle.
- 22. The method of claim 21 wherein the mammal is a human, rat, mouse, canine, bovine, equine, ovine, caprine, or feline.
Statement of Government Support
[0001] The invention was made, at least in part, with a grant from the Government of the United States of America (grant R01 HL36634 from the National Institutes of Health). The Government may have certain rights in the invention.