PAR4 agonist peptides

Patent metadata

Field	Value
Publication number	US-9605024-B2
Application number	US-201615051067-A
Country	US
Kind code	B2
Filing date	Feb 23, 2016
Priority date	Apr 26, 2012
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

Protease activated receptor 4 (PAR4) agonist peptides are disclosed. These peptides are useful for developing robust PAR4 receptor assays.

First claim

What is claimed is:

1. A protease activated receptor 4 (PAR4) agonist peptide comprising an amino acid sequence of Formula I,
Ala-Xaa 1 -Pro-Gly-Xaa 2 -Leu-Val  (Formula I)

wherein,
the amino terminus of the peptide is free;
X aa1 is selected from Tyr and Phe(4-F);
X aa2 is selected from Trp(5-OH), (D,L)-Trp(5-Br), D-Trp, Trp, Bzt, Tpi, His, Tza, 3-Thi, 3-Fur, His(Bzl), Phe, Tyr, Phe(penta-F), 2-Pya, 3-Pya, 4-Pya, Dpa, 3-Pya(4-Tolyl), Bip(2-Methyl), 1-Naphthyl-Ala, 2-Naphthyl-Ala, Tyr(Bzl) and Styryl-Ala; and
the C-terminus of the peptide is amidated.

2. The PAR4 agonist peptide of claim 1 wherein X aa1 is Phe(4-F).

3. The PAR4 agonist peptide of claim 2 wherein X aa2 is Trp.

4. A PAR4 agonist peptide comprising an amino acid sequence of SEQ ID NO: 3, wherein the amino terminus of the peptide is free and the C-terminus of the peptide is amidated.

5. The PAR4 agonist peptide of claim 1 , further comprising Lys after Val.

6. The PAR4 agonist peptide of claim 1 , further comprising Lys-Asn after Val.

7. The PAR4 agonist peptide of claim 1 , further comprising Lys-Asn-Gly after Val.

8. A PAR4 agonist peptide comprising an amino acid sequence of Formula II,
Ala-Xaa 1 -Pro-Gly-Xaa 2 -Leu-Val-Lys  (Formula II)

wherein,
the amino terminus of the peptide is free;
X aa1 is selected from Tyr and Phe(4-F);
X aa2 is selected from Trp(5-OH), (D,L)-Trp(5-Br), D-Trp, Trp, Bzt, Tpi, His, Tza, 3-Thi, 3-Fur, His(Bzl), Phe, Tyr, Phe(penta-F), 2-Pya, 3-Pya, 4-Pya, Dpa, 3-Pya(4-Tolyl), Bip(2-Methyl), 1-Naphthyl-Ala, 2-Naphthyl-Ala, Tyr(Bzl) and Styryl-Ala; and
the C-terminus of the peptide is amidated.

9. The PAR4 agonist peptide of claim 8 wherein X aa1 is Phe(4-F).

10. The PAR4 agonist peptide of claim 8 wherein X aa2 is Trp.

11. A PAR4 agonist peptide comprising an amino acid sequence of Formula III,
Ala-Xaa 1 -Pro-Gly-Xaa 2 -Leu-Val-Lys-Asn  (Formula III)

wherein,
the amino terminus of the peptide is free;
X aa1 is selected from Tyr and Phe(4-F);
X aa2 is selected from Trp(5-OH), (D,L)-Trp(5-Br), D-Trp, Trp, Bzt, Tpi, His, Tza, 3-Thi, 3-Fur, His(Bzl), Phe, Tyr, Phe(penta-F), 2-Pya, 3-Pya, 4-Pya, Dpa, 3-Pya(4-Tolyl), Bip(2-Methyl), 1-Naphthyl-Ala, 2-Naphthyl-Ala, Tyr(Bzl) and Styryl-Ala; and
the C-terminus of the peptide is amidated.

12. The PAR4 agonist peptide of claim 11 wherein X aa1 is Phe(4-F).

13. The PAR4 agonist peptide of claim 11 wherein X aa2 is Trp.

14. A PAR4 agonist peptide comprising an amino acid sequence of Formula IV,
Ala-Xaa 1 -Pro-Gly-Xaa 2 -Leu-Val-Lys-Asn-Gly  (Formula IV)

wherein,
the amino terminus of the peptide is free;
X aa1 is selected from Tyr and Phe(4-F);
X aa2 is selected from Trp(5-OH), (D,L)-Trp(5-Br), D-Trp, Trp, Bzt, Tpi, His, Tza, 3-Thi, 3-Fur, His(Bzl), Phe, Tyr, Phe(penta-F), 2-Pya, 3-Pya, 4-Pya, Dpa, 3-Pya(4-Tolyl), Bip(2-Methyl), 1-Naphthyl-Ala, 2-Naphthyl-Ala, Tyr(Bzl) and Styryl-Ala; and
the C-terminus of the peptide is amidated.

15. The PAR4 agonist peptide of claim 14 wherein X aa1 is Phe(4-F).

16. The PAR4 agonist peptide of claim 14 wherein X aa2 is Trp.

Assignees

• Bristol Myers Squibb Co

Inventors

• Kornacker Michael G
• Mapelli Claudio
• Riexinger Douglas J

Classifications

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D513/04

  Ortho-condensed systems · 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

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title