Peptidomimetics, method of synthesis and uses thereof

Patent metadata

Field	Value
Publication number	US-11472844-B2
Application number	US-201816771114-A
Country	US
Kind code	B2
Filing date	Dec 11, 2018
Priority date	Dec 11, 2017
Publication date	Oct 18, 2022
Grant date	Oct 18, 2022

Abstract

The invention relates to a peptidomimetic comprising or consisting of a D amino-acid sequence having at least 75% identity with SEQ ID NO: 1 or SEQ ID NO: 2, or variants or fragments thereof, in particular a peptidomimetic having the capability to interact at least with: neutrophils and/or neutrophil granules, and/or lactoferrin, and/or globet-cells and/or Muc2 proteins, and/or mucus and/or airway sputum. The peptidomimetic may have the capacity to adopt a multimeric, especially a trimeric, organization, and can be labelled, or associated with a reporter or a carrier entity, or associated with an active molecule. The invention also relates to a Solid-Phase Synthesis method for synthesizing a peptidomimetic of the invention, compositions comprising the same and use of the peptidomimetics as a medicamentor an inflammation marker or a neutrophilic inflammation marker. The invention also relates to the use of a peptidomimetic as a probe or marker for staining purposes, or to detect mucus production, or neutrophils, or to detect or monitor diseases or conditions, especially neutrophilic inflammation. The invention also relates to the use of a polypeptide comprising or consisting of SEQ ID NO: 3, or variants or fragments thereof, as probe or marker for staining lactoferrin, in particular neutrophil lactoferrin, or a probe or marker for investigating neutrophilic inflammation, especially in an imaging method.

First claim

The invention claimed is:

1. A method of detecting lactoferrin, comprising:
a) contacting lactoferrin with a D amino-acid peptidomimetic, wherein the D amino-acid peptidomimetic comprises the amino acid sequence of SEQ ID NO: 1; and
b) detecting the D amino-acid peptidomimetic bound to the lactoferrin.

2. The method of claim 1 , wherein the D amino-acid peptidomimetic comprises the amino acid sequence of SEQ ID NO: 2.

3. The method of claim 2 , wherein the D amino-acid peptidomimetic consists of the amino acid sequence of SEQ ID NO: 2.

4. The method of claim 1 , wherein the D amino-acid peptidomimetic further comprises a label and/or a reporter or a carrier entity, and/or is associated with an active molecule.

5. The method of claim 4 , wherein the D amino-acid peptidomimetic is labelled by coupling with a fluorophore or a biotin.

6. The method of claim 1 , wherein the D amino-acid peptidomimetic has the capacity to adopt a multimeric organization and/or is a trimer.

7. The method of claim 1 , wherein the D amino-acid peptidomimetic has a D-Cysteine residue at its extremity-terminus.

8. The method of claim 1 , wherein the D amino-acid peptidomimetic has an amide group at its C-terminus and/or an acetyl group at its N-terminus.

9. The method of claim 1 , wherein the lactoferrin is present in a patient sample or in a patient (in vivo).

10. The method of claim 9 , wherein lactoferrin associated with neutrophils is detected.

11. The method of claim 9 , wherein lactoferrin associated with neutrophil granules is detected.

12. The method of claim 9 , wherein lactoferrin associated with mucus is detected.

13. The method of claim 9 , wherein lactoferrin secreted by neutrophils that is detected.

14. The method of claim 9 , wherein the presence of detected lactoferrin indicates neutrophilic inflammation.

15. The method of claim 9 , wherein the method comprises administering the D amino-acid peptidomimetic to the patient.

16. The method of claim 9 , wherein the patient has or is suspected to have a pathogen infection.

17. The method of claim 16 , wherein the pathogen infection is a bacterial infection.

18. The method of claim 9 , wherein the patient has or is suspected to have a neoplastic disease.

19. The method of claim 18 , wherein the neoplastic disease is selected from mucinous carcinoma, gastric cancer and colorectal cancer.

20. The method of claim 9 , wherein the patient has or is suspected to have cystic fibrosis.

21. The method of claim 9 , wherein the patient has or is suspected to have an intestine inflammatory disease.

22. The method of claim 9 , wherein the sample comprises living cells.

23. The method of claim 1 , wherein the lactoferrin is glycosylated.

24. The method of claim 1 , wherein the lactoferrin is one or more of glycosylated lactoferrin, neutrophil lactoferrin stored in neutrophil specific granules (β1), neutrophil lactoferrin stored in tertiary granules (β2), and lactoferrin secreted by neutrophils.

Assignees

• Pasteur Institut
• Inst Nat Sante Rech Med
• Centre Nat Rech Scient

Inventors

• Marteyn Benoit Sebastien
• Coic Yves-Marie
• Baleux Francoise

Classifications

• 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

• C07K14/335 Primary

  from Lactobacillus (G) · CPC title

• G01N2333/4725

  Mucins, e.g. human intestinal mucin · CPC title

• C07K1/10

  using coupling agents {(C07K1/006 takes precedence)} · CPC title

• G01N2001/302

  Stain compositions · CPC title