IMPROVED PEPTIDYL CALCINEURIN INHIBITORS

• US 20170281723A1
• Filed: 08/27/2015
• Published: 10/05/2017
• Est. Priority Date: 08/27/2014
• Status: Active Grant

• Current Assignee: Ohio State Innovation Foundation (Ohio State University)
• Original Assignee: Ohio State Innovation Foundation (Ohio State University)
• Inventors: Pei, Dehua, Qian, Ziqing
• Granted Patent: US 10,456,443 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

Improved calcineurin inhibitors and methods of using these improved calcineurin inhibitors to inhibit calcineurin-NFAT signaling in cells and in subjects are disclosed.

Claims

1. A composition, comprising a peptide or peptidomimetic 7 to 100 amino acids in length comprising the amino acid sequence SEQ ID NO:

1, and wherein the composition inhibits calcineurin-NFAT signaling.

2. The composition of claim 1, wherein the peptide or peptidomimetic comprises the amino acid sequence SEQ ID NO:

2.

3. The composition of claim 1, wherein the peptide or peptidomimetic comprises the amino acid sequence SEQ ID NO:

3.

4. The composition of claim 1, wherein the peptide or peptidomimetic comprises the amino acid sequence SEQ ID NO:

4.

5. The composition of claim 1, wherein the peptide or peptidomimetic comprises an amino acid sequence selected from the group consisting of SEQ NOs:

33-46.

6. The composition of claim 1, further comprising a cell penetrating moiety.

7. The composition of claim 6, wherein the cell penetrating moiety is linked to the N-terminus or C-terminus of the peptide or peptidomimetic.

8. The composition of claim 6, wherein the cell penetrating moiety comprises a polyarginine peptide.

9. The composition of claim 6, wherein the cell penetrating moiety comprises a cyclic peptide having an amino acid sequence selected from the group consisting of SEQ ID NO:

8 to SEQ ID NO;

32.

10. A method for inhibiting CN-NFAT signaling in a cell, comprising contacting the cell with the composition of claim 1.

11. A method for treating a disease involving elevated CN-NFAT signaling in a subject, comprising administering to a subject in need thereof a composition of claim 1.