Small molecule composite surfaces as inhibitors of protein-protein interactions

Patent metadata

Field	Value
Publication number	US-9260484-B2
Application number	US-201214126343-A
Country	US
Kind code	B2
Filing date	Jun 15, 2012
Priority date	Jun 15, 2011
Publication date	Feb 16, 2016
Grant date	Feb 16, 2016

Abstract

A method of inhibiting a binding event between a target protein and a binding protein, comprising administering to a cell in vitro an effective amount of a non-naturally occurring bifunctional inhibitor molecule including (a) protein binding moiety, and (b) an effector region, wherein the protein binding moiety binds to a blocking protein, and wherein the effector region binds to the target protein in order to bind the target protein and the blocking protein and prevent access of the binding protein to the target protein. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1. A compound comprising (a) a protein binding moiety and (b) an effector region, wherein said protein binding moiety binds to a blocking protein, and wherein said effector region binds to a target protein, and further wherein the protein binding moiety is:

wherein R 1 is D-β-homoPhe; R 2 is L-Thr; R 3 is L-Ala; and R 4 is L-Ala.

2. A method of inhibiting a binding event between a target protein and a binding protein, comprising:
administering to a cell in vitro an effective amount of the compound of claim 1 .

3. The method of claim 2 , wherein said blocking protein is FKBP.

4. The method of claim 2 , wherein the molecule is a cyclic molecule.

5. The method of claim 2 , wherein the target protein is K-Ras.

6. A library comprising a multiplicity of bifunctional inhibitor molecules, each of said molecules comprising (a) a protein binding moiety and (b) an effector region, wherein said protein binding moiety binds to a blocking protein, and wherein said effector region binds to a target protein, and further wherein the protein binding moiety is:

wherein R 1 is D-β-homoPhe; R 2 is L-Thr; R 3 is L-Ala; and R 4 is L-Ala.

7. A method of preparing the compound of claim 1 , the method comprising the step of covalently bonding the protein binding moiety to the effector region.

8. The method of claim 7 , wherein the effector region is generated randomly prior to the bonding step.

9. A method of treating a patient having a disorder comprising the step of administering the compound of claim 1 in an amount effective to treat the disorder in the patient.

Assignees

• Briesewitz Roger
• Pei Dehua
• Wu Xianghong
• Ohio State Innovation Foundation

Inventors

• Briesewitz Roger
• Pei Dehua
• Wu Xianghong

Classifications

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · 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

• C07K11/02 Primary

  cyclic, e.g. valinomycins {; Derivatives thereof} · CPC title