Methods and compositions related to inhibition of viral entry

Patent metadata

Field	Value
Publication number	US-11020482-B2
Application number	US-201916547383-A
Country	US
Kind code	B2
Filing date	Aug 21, 2019
Priority date	Mar 28, 2011
Publication date	Jun 1, 2021
Grant date	Jun 1, 2021

Abstract

Disclosed herein are compositions and methods for inhibiting viral entry.

First claim

What is claimed is:

1. A method for inhibiting human immunodeficiency virus (HIV) entry into a cell comprising exposing HIV to a composition comprising:
at least three D-peptides and at least one potency-enhancing cargo molecule linked to a tetrameric scaffold, wherein:
each D-peptide comprises the sequence of SEQ ID NO:37 (CDYPEWQWLC); and the potency-enhancing cargo molecule is a membrane localizing potency enhancing cargo molecule selected from the group consisting of a cholesterol or an analog thereof, alkane chain, and a fatty acid, and the membrane localizing potency-enhancing cargo molecule is linked to the tetrameric scaffold via a polyethylene glycol (PEG) linker comprising 12 to 132 PEG units
thereby inhibiting HIV entry into the cell.

2. A method of treating HIV infection in a subject comprising administering to the subject an effective amount of a composition comprising:
at least three D-peptides and at least one potency-enhancing cargo molecule linked to a tetrameric scaffold, wherein:
each D-peptide comprises the sequence of SEQ ID NO:37 (CDYPEWQWLC); and the potency-enhancing cargo molecule is a membrane localizing potency enhancing cargo molecule selected from the group consisting of a cholesterol or an analog thereof, alkane chain, and a fatty acid, and the membrane localizing potency-enhancing cargo molecule is linked to the tetrameric scaffold via a polyethylene glycol (PEG) linker comprising 12 to 132 PEG units.

3. The method of claim 2 , wherein the potency-enhancing cargo molecule is cholesterol or thiocholesterol.

4. The method of claim 2 , wherein the potency-enhancing cargo molecule is an alkane chain.

5. The method of claim 4 , wherein the potency-enhancing cargo molecule is a C8 alkane, a C16 alkane, or a C18 alkane.

6. The method of claim 2 , wherein the potency-enhancing cargo molecule is a fatty acid.

7. The method of claim 6 , wherein the potency-enhancing cargo molecule is a C8 fatty acid, a C16 fatty acid, or a C18 fatty acid.

8. The method of claim 2 , wherein each D-peptide is identical.

9. The method of claim 2 , wherein at least two D-peptides are different.

10. The method of claim 2 , wherein at least one D-peptide comprises the amino acid sequence of any one of SEQ ID NOS:6 and 23-29.

11. The method of claim 2 , wherein each D-peptide comprises an amino acid sequence of SEQ ID NO:26.

12. The method of claim 2 , wherein the tetrameric scaffold is a heterotetrameric scaffold comprising three NHS ester groups and a fourth orthogonal group, wherein the at least three D-peptides are linked to the heterotetrameric scaffold via the three NHS ester groups and the potency-enhancing cargo molecule is linked to the heterotetrameric scaffold via the fourth orthogonal group, wherein the fourth orthogonal group comprises the PEG linker comprising 12 to 132 PEG units.

13. The method of claim 2 , wherein the PEG linker is PEG12, PEG16, PEG24, PEG25, PEG26, PEG27, PEG28, PEG29, PEG30, PEG31, PEG32, PEG33, PEG34, PEG35, PEG36, PEG57 or PEG132.

14. The method of claim 2 , wherein the tetrameric scaffold comprises a tris, di-lysine, benzene ring, phosphate, or peptide core.

15. The method of claim 12 , wherein the potency enhancing cargo molecule is joined to the PEG linker via a reactive group.

16. The method of claim 15 , wherein the reactive group is a maleimide reactive group.

17. The method of claim 12 , wherein the tetrameric scaffold comprises a structure as follows:

18. The method of claim 2 , wherein the composition further comprises a pharmaceutically acceptable carrier.

19. The method of claim 2 , further comprising administering to the subject an antiviral agent or agents selected from the group consisting of a viral replication inhibitor, a viral protease inhibitor, a viral reverse transcriptase inhibitor, a viral entry inhibitor, a viral integrase inhibitor, a viral Rev inhibitor, a viral Tat inhibitor, a viral Nef inhibitor, a viral Vpr inhibitor, a viral Vpu inhibitor, and a viral Vif inhibitor.

Assignees

• Univ Utah Res Found
• The Univ Of Utah Research Foundation

Inventors

• Francis J Nicholas
• Redman Joseph S
• Kay Michael S

Classifications

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K38/10

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K38/08 Primary

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title