Supramolecular hydrogel of fmlf-based molecules and use thereof

Patent metadata

Field	Value
Publication number	US-2017007696-A1
Application number	US-201415115385-A
Country	US
Kind code	A1
Filing date	May 29, 2014
Priority date	Feb 3, 2014
Publication date	Jan 12, 2017
Grant date	—

Abstract

The invention relates to the application of peptides that can self-assemble to form supramolecular nanofibrils and hydrogels, hydrogel compositions containing the self-assembled supramolecular nanofibrils, and methods of uses and making the hydrogel compositions.

First claim

1 . A peptide comprising up to about 35 amino acids, said amino acids having a formylated or acetylated N-terminal residue and a C-terminal residue selected from the group of 2-Nal or 2-Nal D .

2 . The peptide according to claim 1 , wherein the amino acids are all D-amino acids.

3 . The peptide according to claim 1 , wherein the amino acids are a mixture of L-amino acids and D-amino acids.

4 . The peptide according to claim 1 , wherein the formylated N-terminal residue is f-Met or f-Ala.

5 . The peptide according to claim 1 , wherein said C-terminal residue is 2-Nal D .

6 . The peptide according to claim 5 , wherein said peptide exhibits enhanced resistance to proteinase digestion compared to an identical peptide lacking the C-terminal 2-Nal D residue.

7 . The peptide according to claim 6 , wherein said proteinase is proteinase K.

8 - 11 . (canceled)

12 . The peptide according to claim 1 , wherein said peptide is up to about 10 amino acids.

13 - 15 . (canceled)

16 . The peptide according to claim 1 , wherein said peptide is selected from the group consisting of f-MLF-(2-Nal), f-MLF-(2-Nal D ), f-ML-(2-Nal)-(2-Nal D ), f-MIVIL-(2-Nal), f-MIVIL-(2-Nal D ), f-MIFL-(2-Nal), f-MIFL-(2-Nal D ), f-MFINRWLFS-(2-Nal), f-MFINRWLFS-(2-Nal D ), f-MFFINILTL-(2-Nal), f-MFFINILTL-(2-Nal D ), f-AWKYMV D -(2-Nal), f-AWKYMV D -(2-Nal D ), f-M D L D F D -(2-Nal D ), f-M D L D -(2-Nal D )-(2-Nal D ), f-M D I D V D I D L D -(2-Nal D ), f-M D I D F D L D -(2-Nal D ), f-M D F D I D N D R D W D L D F D S D -(2-Nal D ), f-M D F D F D I D N D I D L D T D L D -(2-Nal D ), f-A D W D K D Y D M D V D -(2-Nal D ), Ac-ML-(2-Nal)-(2- Nal D ), and Ac-M D L D -(2-Nal)-(2-Nal D ).

17 . The peptide according to claim 5 , wherein said C-terminal 2-Nal D residue is further connected to a Tn antigen through a serine residue or at a side chain through a ε-amine of a lysine residue.

18 . (canceled)

19 . An immunogenic conjugate comprising an antigenic peptide conjugated to the peptide according to claim 1 .

20 . The immunogenic conjugate according to claim 19 , wherein the antigenic peptide comprises an epitope that induces an antibody mediated immune response.

21 . The immunogenic conjugate according to claim 19 , wherein the antigenic peptide comprises an epitope that induces a T-cell mediated immune response.

22 . A hydrogel composition comprising an aqueous medium and a peptide according to claim 1 , wherein the peptide self assembles to form nanofibrils.

23 - 24 . (canceled)

25 . The hydrogel composition according to claim 22 further comprising an agent selected from the group consisting of an antibiotic agent, a chemotherapeutic agent, an immunotherapeutic agent, and an antigenic agent that comprises an epitope that induces either an antibody mediated or T-cell mediated immune response.

26 . A method for eliciting a prolonged inflammatory response in a subject comprising:
administering to a subject in need thereof a therapeutically effective amount of the hydrogel composition according to claim 22 .

27 . (canceled)

28 . A method for inducing prolonged neutrophil accumulation in vivo comprising:
administering to a subject in need thereof a therapeutically effective amount of the hydrogel composition according to claim 22 , wherein said administering is effective to release the formyl peptide over a period of time exceeding from about 12 hours, thereby inducing prolonged neutrophil accumulation at the site of administration.

29 . (canceled)

30 . A method for treating a cancerous condition comprising:
administering to a subject having a cancerous condition a therapeutically effective amount of the hydrogel composition according to claim 22 , wherein said administering is effective to inhibit tumor growth or shrink tumor size.

31 . (canceled)

32 . A method of treating a bacterial infection comprising:
administering to a patient having a bacterial infection a therapeutically effective amount of the hydrogel composition according to claim 22 , wherein said administering is effective to treat the bacterial infection.

33 - 34 . (canceled)

35 . A method of making a hydrogel composition comprising introducing a peptide according to claim 1 into an aqueous medium, wherein the peptide self-assembles for form nanofibrils.

36 - 110 . (canceled)

Assignees

• Univ Brandeis
• Boston Children'S Hospital

Inventors

• Zhao Fan
• Li Jingyu
• Luo Hongbo R
• Xu Bing

Classifications

• A61K2039/575

  humoral response · CPC title

• A61K38/06

  Tripeptides · CPC title

• A61K38/07

  Tetrapeptides · CPC title

• A61K38/10

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title