Self-assembling peptide and peptide gel with high strength

Abstract

Provide are a peptide gel with practically sufficient mechanical strength and a self-assembling peptide capable of forming the peptide gel. The self-assembling peptide is formed of the following amino acid sequence: a 1 b 1 c 1 b 2 a 2 b 3 db 4 a 3 b 5 c 2 b 6 a 4 where: a 1 to a 4 each represent a basic amino acid residue; b 1 to b 6 each represent an uncharged polar amino acid residue and/or a hydrophobic amino acid residue, provided that at least five thereof each represent a hydrophobic amino acid residue; c 1 and c 2 each represent an acidic amino acid residue; and d represents a hydrophobic amino acid residue.

1 . A self-assembling peptide, comprising an amino acid sequence:
   a 1 b 1 c 1 b 2 a 2 b 3 db 4 a 3 b 5 c 2 b 6 a 4 ,   wherein   a 1  to a 4  each represent a basic amino acid residue,   b 1  to b 6  each represent at least one selected from the group consisting of an uncharged polar amino acid residue and a hydrophobic amino acid residue, provided that at least five thereof each represent a hydrophobic amino acid residue,   c 1  and c 2  each represent an acidic amino acid residue, and   d represents a hydrophobic amino acid residue.   
     
     
         2 . The peptide of  claim 1 , wherein b 3  and b 4  in the amino acid sequence each represent a hydrophobic amino acid residue. 
     
     
         3 . The peptide of  claim 1 , wherein all of b 1  to b 6  in the amino acid sequence each represent a hydrophobic amino acid residue. 
     
     
         4 . The peptide according  claim 1 , wherein b 1  to b 6  in the amino acid sequence each independently represent an alanine residue, a valine residue, a leucine residue, or an isoleucine residue. 
     
     
         5 . The peptide according  claim 1 , wherein d in the amino acid sequence represents an alanine residue, a valine residue, a leucine residue, or an isoleucine residue. 
     
     
         6 . The peptide according  claim 1 , wherein the self-assembling peptide comprises a peptide formed of an amino acid sequence of RLDLRLALRLDLR (SEQ ID NO: 1), RLDLRLLLRLDLR (SEQ ID NO: 2), RADLRLALRLDLR (SEQ ID NO: 6), RLDLRLALRLDAR (SEQ ID NO: 7), RADLRLLLRLDLR (SEQ ID NO: 8), RADLRLLLRLDAR (SEQ ID NO: 9), RLDLRALLRLDLR (SEQ ID NO: 10), or RLDLRLLARLDLR (SEQ ID NO: 11). 
     
     
         7 . The peptide according  claim 1 , wherein the self-assembling peptide comprises a peptide formed of an amino acid sequence of RLDLRLALRLDLR(SEQ ID NO: 1) or RLDLRLLLRLDLR(SEQ ID NO: 2). 
     
     
         8 . A modified peptide, comprising the peptide according to  claim 1 ,
 wherein at least one selected from the group consisting of the N-terminal amino group and the C-terminal carboxyl group is modified, and   wherein the modified peptide has a self-assembling ability.   
     
     
         9 . The modified peptide according to  claim 8 , wherein the at least one selected from the group consisting of the N-terminal amino group and the C-terminal carboxyl group has added thereto an amino acid sequence comprising RGD. 
     
     
         10 . A peptide gel, which is formed from an aqueous solution comprising at least one selected from the group consisting of:
 the peptide according to  claim 1  and   a modified peptide comprising:   the peptide of  claim 1 , wherein at least one selected from the group consisting of the N-terminal amino group and the C-terminal carboxyl group is modified, and   wherein the modified peptide has a self-assembling ability.   
     
     
         11 . The peptide gel according to  claim 10 , wherein the aqueous solution further comprises an additive. 
     
     
         12 . The peptide gel according to  claim 11 , wherein the additive comprises at least one selected from the group consisting of a pH adjuster, an amino acid, a vitamin, a saccharide, a polysaccharide, an alcohol, a polyalcohol, a pigment, a bioactive substance, an enzyme, an antibody, DNA, and RNA. 
     
     
         13 . The peptide gel according to  claim 10 , wherein the peptide gel has an absolute value L (g/s) of an amount of change in load per unit time of 0.03 g/s or more in an approximate straight line of values measured from a start of compression to between 8 and 10 seconds in a compression test carried out at a compression speed of 0.05 mm/s with a jig whose tip has a spherical shape with a diameter of 3.2 mm and a curvature radius of 1.6 mm under a temperature condition of 22° C. 
     
     
         14 . A substrate, comprising at least one selected from the group consisting of:
 (i) the peptide according to  claim 1 ,   (ii) a modified peptide, comprising the peptide of  claim 1 , wherein at least one selected from the group consisting of the N-terminal amino group and the C-terminal carboxyl group is modified, and wherein the modified peptide has a self-assembling ability;   (iii) a peptide gel, which is formed from an aqueous solution comprising at least one selected from the group consisting of:
 the peptide of  claim 1 ; and 
 a modified peptide, comprising the peptide of  claim 1 , wherein at least one selected from the group consisting of the N-terminal amino group and the C-terminal carboxyl group is modified, and wherein the modified peptide has a self-assembling ability, 
   wherein the substrate is suitable for a cell culture.   
     
     
         15 . A method for manufacturing a sterile peptide, comprising:
 sterilizing at least one selected from the group consisting of   the peptide according to  claim 1  and   a modified peptide comprising the peptide of  claim 1 , wherein at least one selected from the group consisting of the N-terminal amino group and the C-terminal carboxyl group is modified, and wherein the modified peptide has a self-assembling ability,   under a pressurized condition at 100° C. or more.   
     
     
         16 . A method for manufacturing an article coated with a peptide gel, comprising:
 freezing the peptide gel according to  claim 10 , to obtain a frozen peptide gel;   melting the frozen peptide gel to provide a peptide sol;   coating at least part of a surface of an article with the peptide sol; and   reconstructing a peptide gel from the peptide sol.   
     
     
         17 . The peptide of  claim 2 , wherein all of b 1  to b 6  in the amino acid sequence each represent a hydrophobic amino acid residue. 
     
     
         18 . The peptide of  claim 2 , wherein b 1  to b 6  in the amino acid sequence each independently represent an alanine residue, a valine residue, a leucine residue, or an isoleucine residue. 
     
     
         19 . The peptide of  claim 3 , wherein b 1  to b 6  in the amino acid sequence each independently represent an alanine residue, a valine residue, a leucine residue, or an isoleucine residue. 
     
     
         20 . The peptide of  claim 2 , wherein d in the amino acid sequence represents an alanine residue, a valine residue, a leucine residue, or an isoleucine residue.