IP Library › Patent Application 14032176
Patent Application
App. No. 14/032,176

ANTAGONIST FOR (PRO)RENIN RECEPTOR FOR THE TREATMENT OF HYPERTENSION AND DIABETES

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Patent No.
US None
App. No.
14/032,176
Abstract

Brain prorenin and the (pro)renin receptor (PRR) have a functional role in the development of hypertension. The present disclosure presents functional PRR antagonistic peptides (e.g., PR10, PR20, PR30, and PR40). In addition, modified peptides comprising one or more thioether-bridges that are stable and strong PRR antagonists are also provided. Methods for treating and preventing hypertension, including neurogenic hypertension, and diabetes with a PRR antagonist are also provided.

Claims (22)

1 . A polypeptide comprising an amino acid sequence having at least 70% identity to the amino acid sequence set forth in one of SEQ ID NOs:1-8 and 16-23.

2 . The polypeptide of claim 1 , comprising an amino acid sequence having at least 80% identity to the amino acid sequence set forth in one of SEQ ID NOs:1-8 and 16-23.

3 . The polypeptide of claim 1 , comprising an amino acid sequence having at least 90% identity to the amino acid sequence set forth in one of SEQ ID NOs:1-8 and 16-23.

4 . A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.

5 . A (pro)renin receptor (PRR) antagonist that blocks prorenin from binding to PRR, wherein the PRR antagonist binds to PRR.

6 . The PRR antagonist of claim 5 , wherein the PRR antagonist is a peptide.

7 . The PRR antagonist of claim 6 , wherein the peptide comprises amino acid residues 3, 4, 6, 7, and 18 of SEQ ID NO:2.

8 . The PRR antagonist of claim 7 , wherein the peptide further comprises amino acid residues 8, 10, and 11 of SEQ ID NO:2.

9 . The PRR antagonist of claim 7 , wherein the peptide further comprises a non-standard amino acid.

10 . The PRR antagonist of claim 9 , wherein the non-standard amino acid is dehydroalanine, 2-aminobutyric acid, or dehydrobutyrine.

11 . The PRR antagonist of claim 6 , wherein the peptide comprises a thioether bridge.

12 . A method for treating or preventing a disease or disorder comprising administering an effective amount of one or more PRR antagonists.

13 . The method of claim 12 , wherein the disease or disorder is hypertension, diabetes, diabetic retinopathy, nephropathy, cardiac hypertrophy, vascular or kidney fibrosis.

14 . The method of claim 12 , wherein the PRR antagonist comprises the polypeptide of claim 1 or the PRR antagonist of claim 5 .

15 . A method for reducing blood pressure comprising administering a PRR antagonist.

16 . The method of claim 15 , wherein the PRR antagonist is a PRR-binding peptide.

17 . The method of claim 16 , wherein the PRR antagonist comprises amino acid residues 3, 4, 6, 7, and 18 of SEQ ID NO:2.

18 . The method of claim 17 , wherein the PRR antagonist further comprises amino acid residues 8, 10, and 11 of SEQ ID NO:2.

19 . The method of claim 16 , wherein the PRR antagonist comprises a non-standard amino acid.

20 . The method of claim 19 , wherein the non-standard amino acid is dehydroalanine, 2-aminobutyric acid, or dehydrobutyrine.

21 . The method of claim 16 , wherein the PRR antagonist comprises a thioether bridge.

22 . The method of claim 15 , wherein the administering step is oral, intravenous, or intracerebroventricular.