Modified antimicrobial peptide derived from an arginine-rich domain

Patent metadata

Field	Value
Publication number	US-12084479-B2
Application number	US-202016932372-A
Country	US
Kind code	B2
Filing date	Jul 17, 2020
Priority date	May 27, 2016
Publication date	Sep 10, 2024
Grant date	Sep 10, 2024

Abstract

An antimicrobial peptide, the peptide comprising 2 to 20 variable domains, each variable domain is a sequence of 2 to 20 consecutive basic amino acids, wherein (a) the variable domains are separated from each other by a variable linker, (b) the variable linker can have 1 to 20 any amino acids other than two or more consecutive basic amino acids, and (c) the peptide has no more than 100 amino acids.

First claim

What is claimed is:

1. An antimicrobial peptide, consisting of RRRGRSPRRRTPSPRRRRSQSPRRRRSC (SEQ ID NO: 7) or RRRGRPRRRPPRRRRQPRRRRC (SEQ ID NO: 9); optionally, at least one of the arginine residues in the peptide is D-arginine.

2. The antimicrobial peptide of claim 1 , wherein at least one of the arginine residues is D-arginine.

3. The antimicrobial peptide of claim 2 , wherein the peptide consists of rRrGRPrRrPPrRrRQPrRrRC (SEQ ID NO: 9), in which R is L-arginine and r is D-arginine.

4. The antimicrobial peptide of claim 2 , wherein the peptide consists of rRrGRSPrRrTPSPrRrRSQSPrRrRSC (SEQ ID NO: 7), in which R is L-arginine and r is D-arginine.

5. The antimicrobial peptide of claim 2 , wherein the peptide consists of RrRGRSPRrRTPSPRrRrSQSPRrRrSC (SEQ ID NO: 7), in which R is L-arginine and r is D-arginine.

6. The antimicrobial peptide of claim 1 , wherein the peptide consists of RRRGRPRRRPPRRRRQPRRRRC (SEQ ID NO: 9), in which each of the arginine residues in the peptide is L-arginine.

7. The antimicrobial peptide of claim 1 , wherein the peptide consists of RRRGRSPRRRTPSPRRRRSQSPRRRRSC (SEQ ID NO: 7), in which each of the arginine residues in the peptide is L-arginine.

8. A pharmaceutical composition comprising the antimicrobial peptide of claim 1 and a pharmaceutically acceptable carrier.

9. A method of treating a bacterial infection, the method comprising administering the composition of claim 8 to a subject in need thereof.

10. A chimeric antimicrobial peptide, consisting of RRRGRSPRRRTPSPRRRRSOSPRRRRSC (SEQ ID NO: 7) or RRRGRPRRRPPRRRRQPRRRRC (SEQ ID NO: 9), and an affinity tag, a signal sequence, a ligand, or another antimicrobial peptide or fragment thereof; optionally, at least one of the arginine residues in the peptide is D-arginine.

11. The chimeric antimicrobial peptide of claim 10 , wherein the antimicrobial peptide consists of RRRGRPRRRPPRRRRQPRRRRC (SEQ ID NO: 9), in which each of the arginine residues in the peptide is L-arginine or at least one of the arginine residues is D-arginine.

12. The chimeric antimicrobial peptide of claim 11 , wherein the antimicrobial peptide consists of rRrGRPrRrPPrRrRQPrRrRC (SEQ ID NO: 9), in which R is L-arginine and r is D-arginine.

13. The chimeric antimicrobial peptide of claim 10 , wherein the antimicrobial peptide consists of RRRGRSPRRRTPSPRRRRSQSPRRRRSC (SEQ ID NO: 7), in which each of the arginine residues in the peptide is L-arginine or at least one of the arginine residues is D-arginine.

14. The chimeric antimicrobial peptide of claim 13 , wherein the antimicrobial peptide consists of rRrGRSPrRrTPSPrRrRSQSPrRrRSC (SEQ ID NO: 7), in which R is L-arginine and r is D-arginine.

15. The chimeric antimicrobial peptide of claim 13 , wherein the antimicrobial peptide consists of RrRGRSPRrRTPSPRrRrSQSPRrRrSC (SEQ ID NO: 7), in which R is L-arginine and r is D-arginine.

16. An antimicrobial peptide conjugate, the conjugate consisting of RRRGRSPRRRTPSPRRRRSQSPRRRRSC (SEQ ID NO: 7) or RRRGRPRRRPPRRRRQPRRRRC (SEQ ID NO: 9), and a non-peptide moiety; optionally, at least one of the arginine residues in the peptide is D-arginine.

17. The antimicrobial peptide conjugate of claim 16 , wherein the antimicrobial peptide consists of RRRGRPRRRPPRRRRQPRRRRC (SEQ ID NO: 9), in which each of the arginine residues in the peptide is L-arginine or at least one of the arginine residues is D-arginine.

18. The antimicrobial peptide conjugate of claim 17 , wherein the antimicrobial peptide consists of rRrGRPrRrPPrRrRQPrRrRC (SEQ ID NO: 9), in which R is L-arginine and r is D-arginine.

19. The antimicrobial peptide conjugate of claim 16 , wherein the antimicrobial peptide consists of RRRGRSPRRRTPSPRRRRSQSPRRRRSC (SEQ ID NO: 7), in which each of the arginine residues in the peptide is L-arginine or at least one of the arginine residues is D-arginine.

20. The antimicrobial peptide conjugate of claim 19 , wherein the antimicrobial peptide consists of rRrGRSPrRrTPSPrRrRSQSPrRrRSC (SEQ ID NO: 7), in which R is L-arginine and r is D-arginine.

21. The antimicrobial peptide conjugate of claim 19 , wherein the antimicrobial peptide consists of RrRGRSPRrRTPSPRrRrSQSPRrRrSC (SEQ ID NO: 7), in which R is L-arginine and r is D-arginine.

Assignees

• Academia Sinica

Inventors

• Shih Chiaho
• Chen Heng-Li
• Su Pei-Yi

Classifications

• C12N2730/10133

  Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory · 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

• A61P31/04

  Antibacterial agents · CPC title

• A01N63/50

  Isolated enzymes; Isolated proteins (peptides A01N37/46) · CPC title

• C07K7/08

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