Peptide amphiphiles having improved solubility and methods of using same
AssigneeNanotope, Inc.
InventorsJames F. Hulvat, Mustafa O. Guler
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Abstract
Disclosed herein are novel peptide amphiphile molecules and compositions discovered to possess improved solubility in aqueous buffers which, in turn, facilitates purification required for pharmaceutical applications, particularly for in vivo administration to human patients. In addition, gels of such peptide amphiphile compositions are shown herein to possess unexpectedly superior gelation kinetics and rheological properties, including an increased mechanical stiffness, which better mimics the mechanical properties of natural central nervous system tissues.
Claims28
A molecule having one of the following structures:
- C15H31C(O)-Ser-Leu-Ser-Leu-Ala-Ala-Ala-Glu-Glu-Ile-Lys-Val-Ala-Val-OH (SEQ ID NO:2) or C15H31C(O)-Ser-Leu-Ser-Leu-Ala-Ala-Ala-Asp-Ile-Lys-Val-Ala-Val-OH (SEQ ID NO:4).
A peptide amphiphile molecule that is soluble in aqueous media and affords a gel under physiological conditions, said peptide amphiphile molecule comprising:
- (a) a lipophilic segment selected from the group consisting of a single, linear moiety of the formula Cn−1H2n−1C(O)—, wherein n=6-22, linked to the N-terminus of the peptide via a peptidyl bond;
- (b) a structural peptide segment intermediate to the peptide amphiphile molecule, comprising 3-8 amino acid residues with non-polar side chains, having a propensity for predominantly beta-sheet secondary structure formation;
- and
- (c) a C-terminal, functional peptide segment selected from any one of SEQ ID NOs:24-26, and (Xaa)m-Val-Ala-Val-Lys-Ile-(Xbb)p (SEQ ID NO:28), where m=1 to 5, p=0 to 3, Xaa is selected from the group consisting of aminomalonic acid (Ama), aspartic acid (Asp), aminoadipic acid (Aib), aminoheptanedioic acid (Apm) and gammacarboxyglutamic acid (Gla), and Xbb is selected from any amino acid.
A method of treating a human subject suffering nerve damage comprising the step of administering a composition comprising the peptide amphiphile molecule having the following structure:
- C15H31C(O)-Ser-Leu-Ser-Leu-Ala-Ala-Ala-Glu-Glu-Ile-Lys-Val-Ala-Val-OH (SEQ ID NO:2) under conditions that stimulate neuron regeneration.
A method of treating a human subject suffering nerve damage comprising the step of administering a composition comprising the peptide amphiphile molecule having the following structure:
- C15H31C(O)-Ser-Leu-Ser-Leu-Ala-Ala-Ala-Asp-Ile-Lys-Val-Ala-Val-OH (SEQ ID NO:4) under conditions that stimulate neuron regeneration.
Dependencies are inferred from the claim text.