Amphiphilic linear peptide/peptoid and hydrogel comprising the same

Patent metadata

Field	Value
Publication number	US-10071183-B2
Application number	US-201514719674-A
Country	US
Kind code	B2
Filing date	May 22, 2015
Priority date	Mar 31, 2010
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

The present invention provides an amphiphilic linear peptide and/or peptoid as well as a hy-drogel that includes the amphiphilic linear peptide/peptoid. The amphiphilic linear pep-tide/peptoid is capable of forming, a hydrogel. These peptides/peptoids include short amphi-philic sequences with a hydrophobic portion of aliphatic amino acids and at least one acidic, neutral, or basic polar amino acid. The amphiphilic linear peptide/peptoid is build up of non repetitive aliphatic amino acids, which may be in the L- or D-form. A plurality of such pep-tides/peptoids assembles to supramolecular helical fibers and forms peptide hydrogels after assembly: A corresponding hydrogel is formed in aqueous solutions at physiological pH and is thus useful for inter alia cell culture, tissue engineering, and drug release. Such hydrogels which are rigid, biocompatible and entrapping up to 99.9% of water are also well suited for applications utilizing electronic devices.

First claim

The invention claimed is:

1. A hydrogel comprising an amphiphilic peptide capable of forming a hydrogel, the amphiphilic peptide comprising an amphiphilic sequence consisting of that defined in (A), (C), (D) or (E):
(A): a hydrophobic sequence stretch of n non repetitive aliphatic amino acids, such that two aliphatic amino acids coupled to each other are always different from one another, wherein n is an integer from 4 to 6, wherein all or a portion of the aliphatic amino acids of the hydrophobic sequence stretch are arranged in an order of decreasing amino acid size in the direction from N- to C-terminus of the amphiphilic peptide, wherein the size of the aliphatic amino acids is defined as I=L>V>A>G, and a polar moiety linked to said hydrophobic sequence stretch which is acidic, neutral or basic, said polar moiety consisting of m adjacent hydrophilic amino acid, wherein m is 1, wherein said hydrophobic sequence stretch comprises and/or forms the N-terminus of the amphiphilic peptide and said polar moiety consists of one amino acid positioned at the C-terminus of the amphiphilic peptide, and wherein the N-terminus of the amphiphilic sequence carries a protecting group; or
(C): a hydrophobic sequence stretch having a sequence AIVA (SEQ ID NO:54), and a polar moiety linked to said hydrophobic sequence stretch which is acidic, neutral or basic, said polar moiety comprising m adjacent hydrophilic amino acids, wherein m is an integer from 1 to 2, wherein said hydrophobic sequence stretch comprises and/or forms the N-terminus of the amphiphilic peptide and said polar moiety consists of at least one amino acid positioned at the C-terminus of the amphiphilic peptide, and the N-terminus of the amphiphilic sequence carries a protecting group; or
(D): an amphiphilic sequence which is IVAD (SEQ ID NO: 22 or 23), and wherein the N-terminus of the amphiphilic sequence carries a protecting group; or
(E): an amphiphilic sequence consisting of a hydrophobic sequence stretch of two aliphatic amino acids which are arranged in an order of decreasing amino acid size in the direction from N- to C-terminus of the amphiphilic peptide, wherein the size of the aliphatic amino acids is defined as I=L>V>A>G, and one adjacent hydrophilic amino acid, said hydrophobic sequence stretch comprises and/or forms the N-terminus of the amphiphilic peptide, said one hydrophilic amino acid is positioned at the C-terminus of the amphiphilic peptide, and the N-terminus of the amphiphilic sequence carries an acetyl group.

2. The hydrogel of claim 1 , wherein the hydrogel is stable in aqueous solution at ambient temperature for a period of at least 7 days.

3. The hydrogel of claim 1 , wherein the hydrogel is characterized by a storage modulus G′ to loss modulus G″ ratio that is greater than 2.

4. The hydrogel of claim 1 , wherein the hydrogel is characterized by a storage modulus G′ from 100 Pa to 80,000 Pa at a frequency in the range of from 0.02 Hz to 16 Hz.

5. The hydrogel of claim 1 , wherein the hydrogel has a higher mechanical strength than collagen or its hydrolyzed form (gelatin).

6. The hydrogel of claim 1 , comprising fibers of the amphiphilic peptide of claim 1 , said fibers defining a network that is capable of entrapping at least one of a microorganism, a virus particle, a peptide, a peptoid, a protein, a nucleic acid, an oligosaccharide, a polysaccharide, a vitamin, an inorganic molecule, a synthetic polymer, a small organic molecule or a pharmaceutically active compound.

7. The hydrogel of claim 6 , wherein the hydrogel comprises at least one of a microorganism, a virus particle, a peptide, a peptoid, a protein, a nucleic acid, an oligosaccharide, a polysaccharide, a vitamin, an inorganic molecule, a synthetic polymer, a small organic molecule or a pharmaceutically active compound entrapped by the network of fibers of the amphiphilic polymer.

8. The hydrogel of claim 7 , wherein the fibers of the amphiphilic polymer are coupled to the at least one of a microorganism, a virus particle, a peptide, a peptoid, a protein, a nucleic acid, an oligosaccharide, a polysaccharide, a vitamin, an inorganic molecule, a synthetic polymer, a small organic molecule or a pharmaceutically active compound entrapped by the network of fibers of the amphiphilic polymer.

9. The hydrogel of claim 1 , wherein the hydrogel is comprised in at least one of a fuel cell, a solar cell, an electronic cell, a biosensing device, a medical device, an implant, a pharmaceutical composition and a cosmetic composition.

10. The hydrogel of claim 1 for use in at least one of the following: release of a pharmaceutically active compound, medical tool kit, a fuel cell, a solar cell, an electronic cell, tissue regeneration, stem cell therapy and gene therapy.

11. The hydrogel of claim 1 , which is injectable.

12. A method of preparing a hydrogel of claim 1 , the method comprising dissolving the amphiphilic peptide of claim 1 in an aqueous solution.

13. The method of claim 12 , wherein the dissolved amphiphilic peptide and/or peptoid in aqueous solution is further exposed to temperature, wherein the temperature is in the range from 20° C. to 90° C., and/or the amphiphilic peptide is dissolved at a concentration from about 0.01 μg/ml.

14. A surgical implant, or stent, the surgical implant or stent comprising a peptide scaffold, wherein the peptide scaffold is formed by the hydrogel of claim 1 .

15. A pharmaceutical and/or cosmetic composition and/or a biomedical device and/or electronic device comprising the hydrogel of claim 1 .

16. The pharmaceutical and/or cosmetic composition of claim 15 , further comprising a pharmaceutically active compound.

17. The pharmaceutical and/or cosmetic composition of claim 16 , further comprising a pharmaceutically acceptable carrier.

18. A method of tissue regeneration comprising the steps:
a) providing a hydrogel of claim 1 ,
b) exposing said hydrogel to cells which are to form regenerated tissue, and
c) allowing said cells to grow on said hydrogel.

19. The method of claim 18 , which is performed in-vitro or in-vivo.

20. The method of claim 19 , which is performed in vivo, wherein, in step a), said hydrogel is provided at a place in a body where tissue regeneration is intended.

21. The method of claim 20 , wherein said step a) is performed by injecting said hydrogel at a place in the body where tissue regeneration is intended.

22. The hydrogel of claim 1 , comprising the amphiphilic sequence consisting of:
(A): a hydrophobic sequence stretch of n non repetitive aliphatic amino acids, such that two aliphatic amino acids coupled to each other are always different from one another, wherein n is an integer from 4 to 6, wherein all or a portion of the aliphatic amino acids of the hydrophobic sequence stretch are arranged in an order of decreasing amino acid size in the direction from N- to C-terminus of the amphiphilic peptide, wherein the size of the aliphatic amino acids is defined as I=L>V>A>G, and a polar moiety linked to said hydrophobic sequence stretch which is acidic, neutral or basic, said polar moiety consisting of m adjacent hydrophilic amino acid, wherein m is 1, wherein said hydrophobic sequence stretch comprises and/or forms the N-terminus of the amphiphilic peptide and said polar moiety consists of one amino acid positioned at the C-terminus of the amphiphilic peptide, and wherein the N-terminus of the amphiphilic sequence carries a protecting group.

23. The hydrogel of claim 22 , wherein

Assignees

• Agency Science Tech & Res

Inventors

• Hauser Charlotte A E
• Khoe Ulung Gondo Kusumo
• Mishra Archana

Classifications

• C07K5/06052

  Val-amino acid · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• C07K5/06113

  Asp- or Asn-amino acid · 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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title