# US 2020/0399319 A1 · Conformation switchable antimicrobial peptides and methods of using the same

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- Number: US 2020/0399319 A1
- Document ID: US20200399319A1
- Status: Published application
- Kind: A1
- Application number: 16/480,914
- Filed: 2018-01-25
- Published: 2020-12-24
- Earliest claimed: 2017-01-25
- Assignees: The Board of Trustees of the University of Illinois
- Applicants: The Board of Trustees of the University of Illinois
- Inventors: Jianjun Cheng; Lin-Feng Chen; Menghua Xiong; Yan Bao
- Web page: https://patentgrep.com/patent/US20200399319A1

## CPC

- C07K 7/06: having 5 to 11 amino acids
- C07K 14/001: {by chemical synthesis}
- 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)
- C07K 1/1072: {by covalent attachment of residues or functional groups}
- C07K 7/04: Linear peptides containing only normal peptide links
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- 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)

## Abstract

The disclosure provides a class of pH-sensitive, helix/random conformation switchable antimicrobial polypeptide (HRS-AMP) compositions as a single agent to selectively kill bacteria (e.g., H. pylori) under acidic condition in the stomach with diminished bacterial resistance compared to currently used antibiotics. Methods of treating bacterial infections in the stomach are also provided.

## Claims

### Claim 1

An antimicrobial polypeptide comprising Formula I:
wherein
m is 3 to about 50;
n is 5 to about 100;
p is 0 or 10;
q is 0, 1, 2, or 3;
R* is H or a negative charge;
Q is —C(═O)O—, —C(═O)NH—, —NH—C(═O)—, or a direct bond;
L is a carbon-containing linker of at least two atoms in length; and
X is primary amine, a secondary amine, a tertiary amine, or a quaternary ammonium moiety;
wherein the polypeptide adopts a random coil confirmation in solution at a pH of greater than about 6.5, and the polypeptide adopts a helical confirmation in solution at a pH of less than about 3.5.

### Claim 2 (depends on 1)

The polypeptide of claim 1 wherein L is (C2-C12)alkyl, wherein the (C2-C12)alkyl is optionally interrupted with one to five oxygen atoms, sulfur atoms, or a combination thereof, and optionally interrupted with phenyl, cycloalkyl, heterocycle, or heteroaryl.

### Claim 3 (depends on 2)

The polypeptide of claim 2 wherein X is an aliphatic or aromatic quaternary ammonium moiety.

### Claim 4 (depends on 3)

The polypeptide of claim 3 wherein X is —N+(R)3 wherein each R is independently phenyl or a straight chain or branched (C1-C10)alkyl.

### Claim 5 (depends on 4)

The polypeptide of claim 4 wherein the total number of carbon atoms in the three R groups combined is 3 to about 15.

### Claim 6 (depends on 5)

The polypeptide of claim 5 wherein X is:
wherein X is bonded to L at the nitrogen of X to form a quaternary ammonium moiety.

### Claim 7 (depends on 3)

The polypeptide of claim 3 wherein X is an aromatic quaternary ammonium moiety selected from:
wherein R is H or (C1-C10)alkyl.

### Claim 8 (depends on 1)

The polypeptide of claim 1 wherein the polypeptide comprises Formula II:
wherein
m is 3 to about 40; n is 5 to about 80;
p is 0 or 1;
q is 0, 1, 2, or 3;
R* is H or a negative charge;
Q is —C(═O)O—, —C(═O)NH—, —NH—C(═O)—, or a direct bond;
L is a carbon-containing linker of two to twenty atoms in length; and
X is an aliphatic or aromatic quaternary ammonium moiety.

### Claim 9 (depends on 8)

The polypeptide of claim 8 wherein the polypeptide comprises Formula III or Formula IV:
wherein Q1 is O or NH.

### Claim 10 (depends on 1)

The polypeptide of claim 1 wherein the polypeptide comprises Formula V:
wherein m is about 3 to about 40, n is about 5 to about 80, t is about 1 to 8, and R1 and R2 are each independently (C2-C8)alkyl.

### Claim 11 (depends on 1)

The polypeptide of claim 1 wherein L is (C2-C12)alkyl, —CH2-Ph-(CH2)y— wherein y is 1 to about 4, —CH2-Ph-O—(CH2)2—O—(CH2)2—, —CH2-Ph-O—(CH2)2—S—(CH2)2—, —CH2-Ph-O—(CH2)3—O—(CH2)2—, —CH2-Ph-O—(CH2)3—S—(CH2)2—, or —CH2-Ph-O—CH2—CH(S(CH2)2—X)—CH2—S—(CH2)2—.

### Claim 12 (depends on 1)

The polypeptide of claim 1 wherein the polypeptide has low toxicity at neutral pH and has high antibacterial activity against H. pylori in an environment having a pH of less than about 4.4.

### Claim 13 (depends on 1)

A method comprising treating a bacterial infection in the stomach of a subject in need thereof by administering to the subject a therapeutically effective amount of a polypeptide of claim 1, wherein the bacterial infection is thereby treated.

### Claim 14 (depends on 13)

The method of claim 13 wherein the polypeptide is administered orally.

### Claim 15 (depends on 14)

The method of claim 14 wherein the bacterial infection is caused by H. pylori.

### Claim 16 (depends on 15)

The method of claim 15 wherein the subject has been diagnosed with gastritis, a gastric ulcer, or gastric carcinoma.

### Claim 17 (depends on 13)

The method of claim 13 wherein the polypeptide causes killing of less than 50% of commensal bacteria in the ileal contents.

### Claim 18

(canceled)

### Claim 19

(canceled)