Peptide for the delivery of anionic materials

Patent metadata

Field	Value
Publication number	US-12049519-B2
Application number	US-202017437025-A
Country	US
Kind code	B2
Filing date	Mar 9, 2020
Priority date	Mar 8, 2019
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

Provided is a peptide including X-(Xaa1)a-(Xaa2)b-Y-(Xaa3)c-(Xaa4)d-Z, or a salt or amide thereof, in which each of X and Z is independently selected from Asn, Cys, Gln, Gly, Ser, Thr and Tyr; in which one of Xaa1 and Xaa2 is His and the other of Xaa1 and Xaa2 is Arg; in which one of Xaa3 and Xaa4 is His and the other of Xaa3 and Xaa4 is Arg; in which the amino functional group of X is, optionally, acylated; in which the carboxylate functional group of Z is, optionally, amidated; in which Y is selected from Ala and Trp; in which each of a and d is independently an integer from 2 to 4; and each of b and c is independently an integer from 2 to 4. The peptide may be used in therapeutic approaches.

First claim

The invention claimed is:

1. A peptide comprising X-(Xaa 1 ) a -(Xaa2) b -Y-(Xaa3) c -(Xaa4) d -Z, or a salt or amide thereof, wherein:
each of X and Z is independently selected from Asn, Cys, Gln, Gly, Ser, Thr and Tyr;
one of Xaa 1 and Xaa 2 is His and the other of Xaa 1 and Xaa 2 is Arg;
one of Xaa 3 and Xaa 4 is His and the other of Xaa 3 and Xaa 4 is Arg;
the amino functional group of X is optionally acylated;
the carboxylate functional group of Z is optionally amidated;
Y is selected from Ala and Trp;
each of a and d is independently an integer from 2 to 4; and
each of b and c is independently an integer from 2 to 4.

2. The peptide according to claim 1 , wherein each of Xaa 2 and Xaa3 is Arg.

3. The peptide according to claim 1 , wherein each of Xaa 1 and Xaa4 is His.

4. The peptide according to claim 1 , wherein each of a and d is identical and is 2 to 4.

5. The peptide according to claim 4 , wherein each of a and d is 3.

6. The peptide according to claim 1 , wherein each of b and c is identical and is 2 to 4.

7. The peptide according to claim 6 , wherein each of b and c is 3.

8. The peptide according to claim 1 , wherein each of a, b, c and d is 3.

9. The peptide according to claim 1 , wherein each of X and Z is identical and selected from Asn, Cys, Gln, Gly, Ser, Thr and Tyr.

10. The peptide according to claim 1 , wherein each of X and Z is Cys.

11. The peptide according to claim 1 , wherein Y is Trp.

12. The peptide according to claim 1 , wherein the sum of b and c is at least six.

13. The peptide according to claim 1 , wherein the sum of a and d is at least six.

14. The peptide according to claim 1 , wherein each of X and Z is Cys; each of Xaa 1 and Xaa 4 is His; each of a and d is independently an integer from 2 to 4; each of Xaa 2 and Xaa 3 is Arg; each of b and c is independently an integer from 2 to 4; and Y is Trp.

15. The peptide according to claim 1 , wherein the net positive charge of the peptide is 6 to 8.

16. The peptide according to claim 15 , wherein the net positive charge of the peptide is 6.

17. The peptide according to claim 1 , wherein the peptide is CHHHHRRRWRRRHHHC (SEQ ID NO: 4).

18. The peptide according to claim 1 , wherein the peptide is 11-20 amino acids in length.

19. A method of delivering an anionic cargo into a cell, wherein the method comprises contacting the cell with a composition comprising a peptide and the anionic cargo, and wherein the peptide consists of the amino acid sequence X-(Xaa 1 ) a -(Xaa2) b -Y-(Xaa3) c -(Xaa4) d -Z, or a salt thereof, wherein:
each of X and Z is independently selected from the group consisting of Asn, Cys, Gln, Gly, Ser, Thr and Tyr;
one of Xaa 1 and Xaa2 is His and the other of Xaa 1 and Xaa2 is Arg;
one of Xaa3 and Xaa4 is His and the other of Xaa3 and Xaa4 is Arg;
the amino functional group of X is optionally acylated;
the carboxylate functional group of Z is optionally amidated;
Y is selected from Ala or Trp;
each of a and d is independently an integer from 2 to 4; and
each of b and c is independently an integer from 2 to 4.

20. A gene therapy method comprising administering to a subject in need thereof a composition comprising a peptide and a therapeutic nucleic acid, and wherein the peptide consists of the amino acid sequence X-(Xaa 1 ) a -(Xaa2) b -Y-(Xaa3) c -(Xaa4) d -Z, or a salt thereof, wherein:
each of X and Z is independently selected from the group consisting of Asn, Cys, Gln, Gly, Ser, Thr and Tyr;
one of Xaa 1 and Xaa2 is His and the other of Xaa 1 and Xaa2 is Arg;
one of Xaa3 and Xaa4 is His and the other of Xaa3 and Xaa4 is Arg;
the amino functional group of X is optionally acylated;
the carboxylate functional group of Z is optionally amidated;
Y is selected from Ala or Trp;
each of a and d is independently an integer from 2 to 4; and
each of b and c is independently an integer from 2 to 4.

21. The method of claim 20 , wherein the method is for treating infection, cancer, or a wound.

22. The method of claim 21 , wherein the cancer is selected from the group consisting of breast cancer, prostate cancer, brain cancer, lung cancer, pancreatic cancer, ovarian cancer and skin cancer.

Assignees

• Univ Belfast

Inventors

• Mccarthy Helen
• Dunne Nicholas
• Robson Tracy
• Mcerlean Emma
• Mulholland Eoghan
• Cole Grace

Classifications

• C12N15/87

  Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation · CPC title

• C07K2318/20

  Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics · CPC title

• A61P35/00

  Antineoplastic agents · 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

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title