Ionic self-assembling peptides
Provided herein are ionic self-assembling peptides, pharmaceutical compositions comprising the peptides, and methods of using and making the same.
1 . A method of making a self-assembling peptide, wherein the self-assembling peptide comprises the amino acid sequence set forth in SEQ ID NO: 15, wherein the method comprises synthesizing the self-assembling peptide by an automated peptide synthesizer and providing the self-assembling peptide in a powder or a solution form.
2 . The method of claim 1 , comprising including in the peptide one or both of,
a) an N-terminal functional group selected from the group consisting of an acetyl, a formyl, pyroglutamyl (pGlu), biotin, polyethylene glycol (PEG), urea, alkylamine, a carbamate, a sulfonamide, dansyl, 2,4-dintrophenyl, fluorescein, 7-methoxycoumarin acetic acid, 9-fluorenylmethyloxycarbonyl, succinyl, chloroacetyl, maleimide, benzyloxycarbonyl, bromoacetyl, nitrilotriacetyl, tertbutoxycarbonyl, 4-hydroxyphenylpropionic acid, allyloxycarbonyl, a fatty acid, and trityl, and
b) a C-terminal functional group selected from the group consisting of an amine, an amido, an N-alkyl amide, an aldehyde, an ester, an alcohol, para-nitroanilide (pNA), 7-amino-4-methylcoumarin (Amc), a hydrazide, hydroxamic acid, chloromethylketone, p-nitroaniline, para-nitrophenol, fluoromethylketone, and cysteamide.
3 . A method of making a pharmaceutical composition, comprising adding a self-assembling peptide in the powder form to water according to claim 1 or providing the self-assembling peptide according to claim 1 in aqueous solution.
4 . The method of claim 3 , comprising adding a tonicity agent wherein the tonicity agent comprises: one or more salts selected from the group consisting of NaCl, KCl, MgCl 2 , CaCl 2 ), NH 4 Cl, Na 2 HPO 4 , KH 2 PO 4 , and CaSO 4 ; and/or
one or more sugars selected from the group consisting of dextrose, mannitol, glycerin, sucrose, and trehalose.
5 . The method of claim 4 , wherein the tonicity agent comprises one or more salts and is present in a concentration of about 0.01 M to about 0.3 M.
6 . The method of claim 4 , wherein the tonicity agent comprises one or more sugars and is present in a concentration of about 0.1-10% (w/v).
7 . The method of claim 3 , wherein the pharmaceutical composition has a pH of from about 6 to about 8.
8 . The method of claim 7 , wherein the net charge of the self-assembling peptide in the pharmaceutical composition is greater than or equal to +1 or less than or equal to −1.
9 . The method of claim 3 , wherein the concentration of the self-assembling peptide in the pharmaceutical composition is from about 0.01% (w/v) to about 10% (w/V).
10 . The method of claim 3 , wherein the pharmaceutical composition further comprises an isolated cell.
11 . The method of claim 10 , wherein the isolated cell is a mammalian cell selected from the group consisting of: an immune cell, a stem cell, chondrocyte progenitor cells, pancreatic progenitor cells, myoblasts, fibroblasts, keratinocytes, neuronal cells, glial cells, pre-adipocytes, adipocytes, vascular endothelial cells, endothelial progenitor cells, mesenchymal cells, smooth muscle progenitor cells, cardiac myocytes, epidermal keratinocytes, and capillary endothelial cells.
12 . The method of claim 3 , wherein the pharmaceutical composition further comprises a bioactive agent.
13 . The method of claim 12 , wherein the bioactive agent is selected from the group consisting of a hormone, an enzyme, an siRNA, an shRNA, an antisense-RNA, an antibiotic, an antibody, and an anti-inflammatory agent.
14 . The method of claim 3 , wherein the pharmaceutical composition is an aqueous solution.
15 . The method of claim 3 , wherein the pharmaceutical composition is a hydrogel.
16 . The method of claim 15 , wherein the hydrogel is characterized by having a storage modulus of at least 10 Pascal (Pa).
17 . The method of claim 3 , comprising providing the pharmaceutical composition in an article of manufacture, wherein the article is a syringe, a vial, an auto-injector, tubing, or a catheter.