Peptidomimetic macrocycles

• US 10,022,422 B2
• Filed: 04/07/2016
• Issued: 07/17/2018
• Est. Priority Date: 01/14/2009
• Status: Active Grant

• Current Assignee: Aileron Therapeutics Inc.
• Original Assignee: Allero Therapeutics BV
• Inventors: Nash, Huw M., Annis, David Allen
• Primary Examiner(s): Ha, Julie
• Application Number:
  US15/093,373
• Publication Number:
  US 20160250278A1
• Time in Patent Office: 831 Days
• Field of Search: 530300, 530323, 514 37
• CPC Class Codes: A61K 38/00 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 Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C07K 7/54 with at least one abnormal peptide link in the ring
• CPC Class Codes: C07K 7/56 the cyclisation not occurring through 2,4-diamino-butanoic acid
• CPC Class Codes: C07K 7/64 Cyclic peptides containing only normal peptide links
• CPC Class Codes: C12N 2760/16022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Novel peptidomimetic macrocycles and methods of using such macrocycles for the treatment of viral diseases are described.

Claims

1. A composition comprising:

a) a peptidomimetic macrocycle comprising an amino acid sequence wherein two amino acids in the amino acid sequence are cross-linked by a crosslinker, wherein the crosslinker comprises a 1, 5-disubstituted triazole and does not comprise a 1,4-disubstituted triazole;

b) a Cu(I) species; and

c) a Ru(II) species.

2. The composition of claim 1, wherein the peptidomimetic macrocycle comprises a helix.

3. The composition of claim 2, wherein the helix is an alpha helix.

4. The composition of claim 1, wherein the peptidomimetic macrocycle comprises a beta turn.

5. The composition of claim 1, wherein the peptidomimetic macrocycle comprises an α

,α

-disubstituted amino acid.

6. The composition of claim 1, wherein the peptidomimetic macrocycle comprises more than one stabilized secondary structure.

7. The composition of claim 1, wherein the cross-linked amino acids are at position i and i+3 of the peptidomimetic macrocycle.

8. The composition of claim 1, wherein the crosslinker spans one turn of a secondary structure of the peptidomimetic macrocycle.

9. The composition of claim 1, wherein the crosslinker spans two turns of a secondary structure of the peptidomimetic macrocycle.

10. The composition of claim 1, wherein the peptidomimetic macrocycle comprises more than two cross-linked amino acids.

11. The composition of claim 1, wherein the 1, 5-disubstituted triazole has a formula

12. The composition of claim 11, wherein each L₁ and L₂ is independently an alkylene.