Chemical synthesis and screening of bicyclic peptide libraries

Patent metadata

Field	Value
Publication number	US-9868767-B2
Application number	US-201414893203-A
Country	US
Kind code	B2
Filing date	May 23, 2014
Priority date	May 23, 2013
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

Disclosed herein are bicyclic peptide compounds, compositions comprising same, methods for making same, and libraries comprising same. The disclosed compounds, in various aspects, are useful for treating a variety of disorders, including inflammatory disorders, autoimmune disorders, and disorders of uncontrolled cellular proliferation. 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 of Formula I-A:

wherein
X m and X n independently comprise a sequence of 1-10 amino acids;
R 0 is selected from hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, or linker to solid phase support; and
K has a structure represented by a formula:

2. The compound of claim 1 , wherein X m and X n comprise different amino acid sequences.

3. The compound of claim 1 , wherein X m comprises 3-7 residues.

4. The compound of claim 1 , wherein X m comprises 4-6 residues.

5. The compound of claim 1 , wherein X n comprises 2-6 residues.

6. The compound of claim 1 , wherein X n comprises 3-5 residues.

7. The compound of claim 1 , wherein the amino acid residues in X n , X m , or both X n and X m are all natural amino acids.

8. The compound of claim 1 , wherein the compound has a molecular weight of 500-5000.

9. The compound of claim 1 , wherein the compound is of Formula I-A-1:

10. The compound of claim 1 , wherein the compound is of Formula I-A-2:

11. A compound comprising:
a. a residue of trimesic acid, the residue bearing three carboxyl functionalities;
b. a lysine residue covalently bonded to the first carboxyl functionality of the trimesic acid residue;
c. a first peptide chain of 1-10 amino acid residues, X m , covalently bonded to the second carboxyl functionality of the trimesic acid residue and to the lysine residue; and
d. a second peptide chain of 1-10 amino acid residues, X n , covalently bonded to the third carboxyl functionality of the trimesic acid residue and to the lysine residue.

12. The compound of claim 11 , wherein the first peptide chain comprises 3-7 residues.

13. The compound of claim 11 , wherein the second peptide chain comprises 2-6 residues.

14. The compound of claim 11 , wherein all of the residues in the first peptide chain, the second peptide chain, or both the first and second peptide chains are natural amino acids.

15. The compound of claim 11 , wherein the compound has a molecular weight between 500 and 5000.

16. The compound of claim 1 , wherein X m and X n are selected from SEQ ID NO.:“1-4 and 6-63”.

17. The compound of claim 1 , wherein X m and X n are selected from SEQ ID NO.:“1-4 and 6-25”.

18. The compound of claim 11 , wherein X m and X n are selected from SEQ ID NO.:“1-4 and 6-63”.

19. The compound of claim 11 , wherein X m and X n are selected from SEQ ID NO.:“1-4 and 6-25”.

Assignees

• Ohio State Innovation Foundation

Inventors

• Pei Dehua
• Upadhyaya Punit
• Lian Wenlong
• Trinh Thi

Classifications

• 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

• C07K5/0817

  the first amino acid being Arg · CPC title

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• C07K5/06156

  and Trp-amino acid; Derivatives thereof · CPC title

• C07K5/0202 Primary

  containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids · CPC title