Chimeric natriuretic polypeptides with unique pharmacologic profiles
View Patent ↗This document provides natriuretic polypeptides. For example, this document provides polypeptides having a natriuretic activity. In some cases, a polypeptide provided herein can have natriuretic activities without inducing excessive hypotension. This document also provides methods and materials for inducing natriuretic activities within a mammal.
1. A polypeptide less than 44 amino acid residues in length, wherein said polypeptide comprises, in an order from amino terminus to carboxy terminus:
(a) the sequence set forth in SEQ ID NO:6 or the sequence set forth in SEQ ID NO:6 with no more than two additions, subtractions, or substitutions,
(b) the sequence set forth in SEQ ID NO:2 or the sequence set forth in SEQ ID NO:2 with no more than one addition, subtraction, or substitution, and
(c) the sequence set forth in SEQ ID NO:7 or the sequence set forth in SEQ ID NO:7 with no more than two additions, subtractions, or substitutions,
wherein said polypeptide, when administered to a mammal, induces a decrease in mean arterial pressure to a lesser extent than that induced by human BNP, when said human BNP is administered to a mammal.
2. The polypeptide of claim 1 , wherein said polypeptide comprises natriuretic activity.
3. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6, the sequence set forth in SEQ ID NO:2, and the sequence set forth in SEQ ID NO:7.
4. The polypeptide of claim 1 , wherein said polypeptide is a substantially pure polypeptide.
5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polypeptide less than 44 amino acid residues in length, wherein said polypeptide comprises, in an order from amino terminus to carboxy terminus:
(i) the sequence set forth in SEQ ID NO:6 or the sequence set forth in SEQ ID NO:6 with no more than two additions, subtractions, or substitutions,
(ii) the sequence set forth in SEQ ID NO:2 or the sequence set forth in SEQ ID NO:2 with no more than one addition, subtraction, or substitution, and
(iii) the sequence set forth in SEQ ID NO:7 or the sequence set forth in SEQ ID NO:7 with no more than two additions, subtractions, or substitutions,
wherein said polypeptide, when administered to a mammal, induces a decrease in mean arterial pressure to a lesser extent than that induced by human BNP, when said human BNP is administered to a mammal.
6. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6.
7. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6 with no more than two additions, subtractions, or substitutions.
8. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6 with one addition, subtraction, or substitution.
9. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:2.
10. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:2 with one addition, subtraction, or substitution.
11. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7.
12. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7 with no more than two additions, subtractions, or substitutions.
13. The polypeptide of claim 1 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7 with one addition, subtraction, or substitution.
14. The polypeptide of claim 5 , wherein said polypeptide comprises natriuretic activity.
15. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6, the sequence set forth in SEQ ID NO:2, and the sequence set forth in SEQ ID NO:7.
16. The polypeptide of claim 5 , wherein said polypeptide is a substantially pure polypeptide.
17. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6.
18. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6 with no more than two additions, subtractions, or substitutions.
19. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:6 with one addition, subtraction, or substitution.
20. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:2.
21. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:2 with one addition, subtraction, or substitution.
22. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7.
23. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7 with no more than two additions, subtractions, or substitutions.
24. The polypeptide of claim 5 , wherein said polypeptide comprises the sequence set forth in SEQ ID NO:7 with one addition, subtraction, or substitution.