Analogues of VDAC1-derived peptides

Patent metadata

Field	Value
Publication number	US-10829530-B2
Application number	US-201916451520-A
Country	US
Kind code	B2
Filing date	Jun 25, 2019
Priority date	Sep 3, 2015
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

The present invention relates to peptides comprising analogues of VDAC1-derived peptides having improved pharmacokinetic characteristics compared to the native parent peptides, which are effective in impairing cell energy production, in inducing apoptosis and cell death, particularly of cancerous cells, in eliminating cancer stem cells and in reducing symptoms associated with fat accumulation in liver cells particularly with nonalcoholic fatty liver disease (NAFLD) and symptoms associated thereto.

First claim

What is claimed is:

1. A method for treating a disease associated with aberrant apoptosis and/or cell hyper-proliferation, the method comprises administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a synthetic peptide comprising (i) an analogue of a VDAC1-derived peptide, wherein the analogue comprises the amino acid sequence set forth in SEQ ID NO:2 and is completely inverso modified, and (ii) a recognition and/or localization peptide comprising the amino acid sequence set forth in SEQ ID NO:8 to treat the disease, wherein the disease is a cancerous disease selected from the group consisting of glioma, liver cancer, leukemia, lung cancer, breast cancer, prostate cancer, pancreas cancer and melanoma.

2. The method of claim 1 , wherein the recognition and/or localization moiety is an all L-stereomeric peptide or an all D-stereomeric peptide.

3. The method of claim 2 , wherein the recognition and/or localization peptide is connected to the N- or the C-terminus of the analogue of VDAC1-derived peptide directly or via a linker sequence.

4. The method of claim 3 , wherein the synthetic peptide further comprises the amino acid sequence set forth in SEQ ID NO:11 and the amino acid sequence set forth in SEQ NO:12, each independently located at the C- or N-terminus of the analogue of VDAC1-derived peptide.

5. The method of claim 3 , wherein the synthetic peptide further comprises the amino acid sequence set forth in SEQ ID NO:12 and the amino acid sequence set forth in SEQ ID NO:13, each independently located at the C- or N-terminus of the analogue of VDAC1-derived peptide.

6. The method of claim 5 , wherein the synthetic peptide comprises the amino acid sequence set forth in SEQ ID NO:14.

7. The method of claim 1 , wherein the cancerous disease is a glioma.

8. The method of claim 7 , wherein the glioma is a glioblastoma.

Assignees

• B G Negev Technologies And Applications Ltd At Ben Gurion Univ
• Nat Inst Biotechnology Negev Ltd
• The National Institute For Biotechnology In The Negev Ltd Ben Gurion Univ Of The Negev

Inventors

• Shoshan-Barmatz Varda

Classifications

• C07K2319/10

  containing a tag for extracellular membrane crossing, e.g. TAT or VP22 · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/79

  Transferrins, e.g. lactoferrins, ovotransferrins · CPC title

• C07K14/4747 Primary

  Apoptosis related proteins · CPC title

• C07K14/08 Primary

  RNA viruses · CPC title