Nemo coiled coil mimics and methods of using same

Patent metadata

Field	Value
Publication number	US-12371461-B2
Application number	US-202217723921-A
Country	US
Kind code	B2
Filing date	Apr 19, 2022
Priority date	Nov 16, 2018
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

This invention relates to macrostructures (and pharmaceutical formulations containing them) that include a parallel coiled-coil structure, wherein the parallel coiled-coil comprises a first coil of Formula I and a second coil of Formula II:

T 1 -f 0 -g 0 -a 1 -b 1 -c 1 -d 1 -e 1 -f 1 -g 1 -a 2 -b 2 -c 2 -d 2 -e 2 -f 2 -g 2 -a 3 -b 3 -c 3 -d 3 -e 3 -T 2   (I)

T 3 -g′ 0 -a′ 1 -b′ 1 -c′ 1 -d′ 1 -e′ 1 -f′ 1 -g′ 1 -a′ 2 -b′ 2 -c′ 2 -d′ 2 -e′ 2 -f′ 2 -g′ 2 -a′ 3 -b′ 3 -c′ 3 -d′ 3 -e′ 3 -f′ 3 -T 4   (II),

as described in the present application. Methods of using these macrostructures are also disclosed.

First claim

What is claimed:

1. A method of inhibiting interaction between NEMO and a target molecule that binds to a helix dimer consisting of HLX1 and HLX2 of NEMO, said method comprising:
contacting NEMO and/or the target molecule with a macrostructure comprising a parallel coiled-coil selected from the group consisting of CHD1 NEMO , CHD2 NEMO , CHD3 NEMO , and CHD4 NEMO under conditions effective to inhibit interaction between NEMO and the target molecule, wherein the target molecule is vFLIP.

2. The method of claim 1 , wherein said contacting is carried out in vivo.

3. The method of claim 1 , wherein said contacting is carried out in a cell.

4. The method of claim 1 , wherein said contacting is carried out in a subject.

5. The method of claim 3 , wherein said contacting induces apoptosis of the cell, inhibits proliferation of the cell, and/or inhibits NFκB translocation in the cell.

6. The method of claim 3 , wherein the cells are mammalian cells.

7. The method of claim 3 , wherein the cells are primate cells.

8. The method of claim 3 , wherein the cells are lymphoma cells or Kaposi sarcoma (“KS”) cells.

9. The method of claim 1 , wherein the method is carried out in a subject.

10. The method of claim 1 , wherein the macrostructure comprising the parallel coiled-coil is CHD3 NEMO .

Assignees

• Univ New York
• Univ Cornell

Inventors

• Arora Paramjit S
• Cesarman Ethel
• Wuo Michael G
• Sadek Jouliana

Classifications

• C07C49/04

  Saturated compounds containing keto groups bound to acyclic carbon atoms · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K7/08

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

• C07K7/02

  Linear peptides containing at least one abnormal peptide link · CPC title