Peptide inhibitors targeting the Neisseria gonorrhoeae pivotal anaerobic respiration factor AniA

Patent metadata

Field	Value
Publication number	US-10875890-B2
Application number	US-201816489707-A
Country	US
Kind code	B2
Filing date	Mar 13, 2018
Priority date	Mar 14, 2017
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

Disclosed herein are peptide inhibitors of AniA. Pharmaceutical compositions are also disclosed that include one or more peptide inhibitors of AniA and/or nucleic acids encoding the same. The pharmacological inhibition of AniA should disable anaerobic respiration and augment the ability of existing antimicrobials to clear the pathogen. Thus, also disclosed are methods of inhibiting and/or treating infection from N. gonorrhoeae.

First claim

We claim:

1. An isolated peptide, comprising the amino acid sequence set forth as CX 1 YX 2 RLNLW (SEQ ID NO: 37), wherein X 1 can be a N or S, and wherein X 2 can be a N or S.

2. A composition comprising one or more peptides of claim 1 , and a pharmaceutically acceptable carrier.

3. The composition of claim 2 , further comprising an antibiotic agent.

4. An isolated peptide comprising the amino acid sequence set forth as one of SEQ ID NO: 7, SEQ ID NO: 9, and SEQ ID NO: 10.

5. The isolated peptide of claim 4 , wherein the amino acid sequence further comprises the amino acid sequence GGGS (SEQ ID NO: 38) on the C-terminal end.

6. The isolated peptide of claim 5 , wherein the amino acid sequence is set forth as one of SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

7. A composition comprising one or more peptides of claim 4 , and a pharmaceutically acceptable carrier.

8. The composition of claim 7 , further comprising an antibiotic agent.

9. A method of treating and/or inhibiting Neisseria gonorrhoeae infection in a subject, comprising:
selecting a subject for treatment that has, or is at a risk for developing, an infection by Neisseria gonorrhoeae ; and
administering to a subject a therapeutically effective amount of the composition of claim 7 , thereby treating and/or inhibiting Neisseria gonorrhoeae infection in the subject.

10. The method of claim 9 , wherein the amino acid sequence further comprises the amino acid sequence GGGS (SEQ ID NO: 38) on the C-terminal end.

11. The method of claim 10 , wherein the amino acid sequence is set forth as one of SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

12. A method of inhibiting AniA enzymatic activity in a cell comprising:
contacting a cell expressing AniA with an effective amount of the peptide of claim 4 , thereby inhibiting AniA enzymatic activity in the cell.

13. The method of claim 12 , wherein the amino acid sequence further comprises the amino acid sequence GGGS (SEQ ID NO: 38) on the C-terminal end.

14. The method of claim 13 , wherein the amino acid sequence is the amino acid sequences set forth as one of SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4.

15. The method of claim 12 , further comprising, contacting the cell with an effective amount of an antibiotic for Neisseria gonorrhoeae .

16. The method of claim 12 , wherein the cell is a Neisseria gonorrhoeae cell.

17. A method of treating and/or inhibiting Neisseria gonorrhoeae infection in a subject, comprising:
selecting a subject for treatment that has, or is at a risk for developing, an infection by Neisseria gonorrhoeae ; and
administering to a subject a therapeutically effective amount of the composition of claim 2 , thereby treating and/or inhibiting Neisseria gonorrhoeae infection in the subject.

18. A method of inhibiting AniA enzymatic activity in a cell, comprising:
contacting a cell expressing AniA with an effective amount of the peptide of claim 1 , thereby inhibiting AniA enzymatic activity in the cell.

19. The method of claim 18 , wherein the amino acid sequence further comprises the amino acid sequence GGGS (SEQ ID NO: 38) on the C-terminal end.

20. The method of claim 19 , further comprising, contacting the cell with an effective amount of an antibiotic for Neisseria gonorrhoeae .

Assignees

• Univ Oregon State
• The Univ Of Kentucky Research Foundation

Inventors

• Sikora Aleksandra
• Korotkov Konstantin V

Classifications

• C07K7/06 Primary

  having 5 to 11 amino acids · 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

• G01N33/56911

  Bacteria · CPC title

• A61P31/04

  Antibacterial agents · CPC title