# US 2024/0199698 A1 · Peptide amphiphile compositions and methods of use thereof

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- Number: US 2024/0199698 A1
- Document ID: US20240199698A1
- Status: Published application
- Kind: A1
- Application number: 18/482,740
- Filed: 2023-10-06
- Published: 2024-06-20
- Earliest claimed: 2022-10-10
- Applicants: Uab Research Foundation; Endomimetics LLC
- Inventors: HO-WOOK JUN; BRIGITTA BROTT; XIXI ZHANG; JUN CHEN; JENNIFER SHERWOOD; PATRICK HWANG
- Web page: https://patentgrep.com/patent/US20240199698A1

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/7036: having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
- A61K 38/00: 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)
- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are peptide amphiphiles comprising a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence. In some aspects, the hydrophilic peptide sequence comprises a degrading sequence (DS), wherein the degrading sequence (DS) comprises the amino acid sequence GTAGLIGQ (SEQ ID NO:1) wherein the DS comprises one or more amino acid substitutions. Also disclosed are compositions, liposomes, gels, and medical devices comprising the peptide amphiphiles and methods of use thereof.

## Claims

### Claim 1

A peptide amphiphile comprising a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain or a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence.

### Claim 2 (depends on 1)

The peptide amphiphile of claim 1, wherein the nitric oxide producing donor sequence comprises the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3).

### Claim 3 (depends on 2)

The peptide amphiphile of claim 2, wherein the nitric oxide producing donor sequence comprises the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and wherein one or more of the Lys residues comprise a pendant amine group.

### Claim 4

(canceled)

### Claim 5

(canceled)

### Claim 6 (depends on 1)

A composition comprising the peptide amphiphile of claim 1.

### Claim at position 7

-11. (canceled)

### Claim 12 (depends on 6)

The composition of claim 6, wherein the composition further comprises a pharmaceutically active agent, wherein the pharmaceutically active agent is a therapeutic drug for cardiovascular disease, wherein the therapeutic drug for cardiovascular disease is sirolimus or everolimus, and wherein the peptide amphiphile comprises:
a. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
b. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (1(.5; SEQ ID NO:3) and one cell adhesive sequence comprising the amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
c. a mixture of two peptide amphiphiles,
wherein the first peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises an endothelial cell-adhesive sequence (CA) comprising an amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein the second peptide amphiphile comprises comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and also comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group; or
d. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence, comprising the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and wherein one or more of the Lys residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one of the pendant amine groups.

### Claim 13 (depends on 6)

The composition of claim 6, wherein the composition further comprises a pharmaceutically active agent, wherein the pharmaceutically active agent is a therapeutic drug for cardiovascular disease, wherein the therapeutic drug for cardiovascular disease is colchicine, and wherein the peptide amphiphile comprises:
a. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
b. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (1(.5; SEQ ID NO:3) and one cell adhesive sequence comprising the amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
c. a mixture of two peptide amphiphiles,
wherein the first peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises an endothelial cell-adhesive sequence (CA) comprising an amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein the second peptide amphiphile comprises comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and also comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group; or
d. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence, comprising the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and wherein one or more of the Lys residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one of the pendant amine groups.

### Claim 14 (depends on 6)

The composition of claim 6, wherein the composition further comprises a pharmaceutically active agent, wherein the pharmaceutically active agent is a therapeutic drug for cardiovascular disease, wherein the therapeutic drug for cardiovascular disease is a statin, and wherein the peptide amphiphile comprises:
a. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
b. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (1(.5; SEQ ID NO:3) and one cell adhesive sequence comprising the amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
c. a mixture of two peptide amphiphiles,
wherein the first peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises an endothelial cell-adhesive sequence (CA) comprising an amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein the second peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5;
SEQ ID NO:3) and also comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group; or
c. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence, comprising the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and wherein one or more of the Lys residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one of the pendant amine groups.

### Claim 15

(canceled)

### Claim 16

(canceled)

### Claim 17

(canceled)

### Claim 18 (depends on 6)

The composition of claim 6, wherein the composition further comprises a pharmaceutically active agent, wherein the pharmaceutically active agent is an antibiotic, wherein the antibiotic is gentamicin and wherein the peptide amphiphile comprises:
a. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
b. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (1(5; SEQ ID NO:3) and one cell adhesive sequence comprising the amino acid sequence Arg-Gly-Asp-Ser (RGDS; SEQ ID NO:5), wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
c. PA-C16-K5-YIGSR-NO; a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and further comprising a cell adhesive ligand comprising an amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2), wherein herein one or more of the lysine residues comprise pendant amine groups that react with NO to form a diazeniumdiolate-modified peptide amphiphile;
d. a mixture of two peptide amphiphiles,
wherein the first peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises an endothelial cell-adhesive sequence (CA) comprising an amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein the second peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5;
SEQ ID NO:3) and also comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group; or
e. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence, comprising the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and wherein one or more of the Lys residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one of the pendant amine groups.

### Claim 19 (depends on 6)

The composition of claim 6, wherein the composition further comprises a pharmaceutically active agent, wherein the pharmaceutically active agent is an antibiotic, wherein the antibiotic is vancomycin and wherein the peptide amphiphile comprises:
a. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
b. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (1(.5; SEQ ID NO:3) and one cell adhesive sequence comprising the amino acid sequence Arg-Gly-Asp-Ser (RGDS; SEQ ID NO:5), wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
c. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), and comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and one cell adhesive sequence comprising the amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2), wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group;
d. a mixture of two peptide amphiphiles,
wherein the first peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises an endothelial cell-adhesive sequence (CA) comprising an amino acid sequence Tyr-Ile-Gly-Ser-Arg (YIGSR; SEQ ID NO:2) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein the second peptide amphiphile comprises comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and also comprises a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1),
wherein one or more of the Lys residues of the second peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group; or
e. a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted C5 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence, comprising the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK; SEQ ID NO:3) and wherein one or more of the Lys residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one of the pendant amine groups.

### Claim at position 16

-34. (canceled)

### Claim 35 (depends on 1)

A gel comprising the peptide amphiphile of claim 1.

### Claim 36 (depends on 1)

A medical device coated with a peptide amphiphile of claim 1.

### Claim 37

— 39. (canceled)

### Claim 40 (depends on 6)

A method of preventing infection in a subject comprising administering to the subject a therapeutically effective amount of a composition of claim 6, wherein the composition further comprises a pharmaceutically active agent, wherein the pharmaceutically active agent is an antibiotic to a subject in need thereof.

### Claim 41 (depends on 36)

A method of treating a subject in need thereof comprising administering the medical device of claim 36 to a subject during osseointegration.

### Claim 42 (depends on 35)

A method of increasing vascularization or treating inflammation in a subject comprising administering the gel of claim 35 to a subject in need thereof.

### Claim 43

(canceled)

### Claim 44 (depends on 2)

A method of making the peptide amphiphile of claim 2, wherein the pendant amine groups can react with nitric oxide to form a diazeniumdiolate-modified peptide amphiphile, wherein the diazeniumdiolate is a NO donor and comprises one or more molecule of nitric oxide comprising:
a. obtaining a peptide amphiphile comprising a nitric oxide (NO) producing donor sequence, wherein the peptide amphiphile comprises an N-terminus,
b. alkylating the N-terminus of the peptide amphiphile with a hydrophobic moiety, wherein the alkylation comprises amination with a valeric acid, and
c. conjugating NO to the peptide amphiphile.

### Claim at position 25

-48. (canceled)

### Claim 49 (depends on 1)

A method of treating arteriovenous fistula failure or preventing or treating cardiovascular disease in a subject, comprising administering to the subject a therapeutically effective amount of the peptide amphiphile of claim 1 to a subject in need thereof.

### Claim at position 27

-53. (canceled)

### Claim 54 (depends on 1)

A kit comprising the peptide amphiphile of claim 1.

### Claim 55

A gel comprising a peptide amphiphile, wherein the peptide amphiphile a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having an optionally substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence comprising an amino acid sequence KKKKK (SEQ ID NO:3) and also comprises a degrading sequence (DS) comprising an amino acid sequence GTAGLIGQ (SEQ ID NO:1), wherein one or more of the Lys residues of the peptide amphiphile comprises a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group.

### Claim 56

(canceled)

### Claim 57

A composition comprising a peptide amphiphile, wherein the peptide amphiphile comprises a hydrophilic peptide sequence and a hydrophobic tail, wherein the hydrophobic tail comprises a moiety having a substituted a substituted C16 alkyl chain, wherein the hydrophilic peptide sequence comprises a nitric oxide producing donor sequence wherein the nitric oxide producing donor sequence comprises the amino acid sequence Lys-Lys-Lys-Lys-Lys (KKKKK) (K5; SEQ ID NO:3) and a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1), wherein one or more of the lysine residues comprise a pendant amine group, wherein one or more molecules of nitric oxide is bound to at least one pendant amine group.

### Claim 58 (depends on 1)

The peptide Amphiphile of claim 1, further comprising a degrading sequence (DS) comprising an amino acid sequence Gly-Thr-Ala-Gly-Leu-ILE-Gly-Gln (GTAGLIGQ; SEQ ID NO:1).