Novel antimicrobial agents

Patent metadata

Field	Value
Publication number	US-2016303246-A1
Application number	US-201615186571-A
Country	US
Kind code	A1
Filing date	Jun 20, 2016
Priority date	Sep 27, 2004
Publication date	Oct 20, 2016
Grant date	—

Abstract

A novel class of antimicrobial polymeric agents, which include a plurality of positively charged amino acid residues and at least one omega-amino-fatty acid residue linking therebetween, designed to exert antimicrobial activity while being stable, non-toxic and avoiding development of resistance thereto and a process of preparing same are disclosed. Further disclosed are pharmaceutical compositions containing same and a method of treating medical conditions associated with pathological microorganisms, a medical device, an imaging probe and a food preservative utilizing same. Further disclosed are conjugates of an amino acid residue and a hydrophobic moiety residue and a process of preparing same.

First claim

What is claimed is:

1 . A polymer comprising a plurality of positively charged amino acid residues and at least one hydrophobic moiety residue, wherein at least one of said at least one hydrophobic moiety residue is being covalently linked to at least two amino acid residues in said plurality of amino acid residues via the N-alpha of one amino acid residue and via the C-alpha of the other amino acid residue in said at least two amino acid residues.

2 . The polymer of claim 1 , wherein said plurality of amino acid residues comprises from 2 to 50 amino acid residues.

3 . The polymer of claim 1 , wherein said positively charged amino acid residues are selected from the group consisting of lysine residues, histidine residues, ornithine residues, arginine residues and combinations thereof.

4 . The polymer of claim 1 , wherein said at least one hydrophobic moiety has a carboxylic group at one end thereof and an amine group at the other end thereof.

5 . The polymer of claim 4 , wherein said at least one hydrophobic moiety residue is linked to each of said at least two amino acid residues via a peptide bond.

6 . The polymer of claim 1 , comprising from 1 to 50 hydrophobic moiety residues.

7 . The polymer of claim 1 , wherein said at least one hydrophobic moiety residue comprises a fatty acid residue.

8 . The polymer of claim 1 , wherein each of said at least one hydrophobic moiety is an ω-amino-fatty acid residue.

9 . The polymer of claim 1 , comprising at least two hydrophobic moiety residues, wherein at least one of said at least two hydrophobic moiety residues is being linked to the N-alpha of an amino acid residue at the N-terminus of said plurality of amino acid residues.

10 . The polymer of claim 3 , comprising 2 to 50 lysine residues and 1 to 50 ω-amino-fatty acid residues, wherein:
at least one of said ω-amino-fatty acid residues is covalently linked to at least two of said lysine residues via the N-alpha of one lysine residue and via the C-alpha of the other lysine residue in said at least two lysine residues, said at least one ω-amino-fatty acid is linked to each of said lysine residues via a peptide bond,
and wherein:
each of said lysine residues is independently selected from the group consisting of a lysine residue and a lysine residue having a fatty acid residue linked to a side-chain thereof;
an N-terminus of the polymer is selected from the group consisting of a lysine residue, an ω-amino-fatty acid residue linked via a peptide bond to a lysine residue and a fatty acid residue linked via a peptide bond to said lysine residue; and
a C-terminus of the polymer is selected from the group consisting of a lysine residue and a lysine residue terminated with an amide group.

11 . The polymer of claim 10 , wherein said ω-amino-fatty acid residue is selected from the group consisting of 4-amino-butyric acid residue, 6-amino-caproic acid residue, 8-amino-caprylic acid residue, 10-amino-capric acid residue, 12-amino-lauric acid residue, 14-amino-myristic acid residue, 16-amino-palmitic acid residue, 16-amino-palmitoleic acid residue, 18-amino-stearic acid residue, 18-amino-oleic acid residue, 18-amino-linoleic acid residue, 18-amino-linolenic acid residue and 20-amino-arachidonic acid residue.

12 . The polymer of claim 11 , having an amino acid sequence selected from the group consisting of the amino acid sequences as set forth in SEQ ID NOs: 1-83 and 86-94 as set forth herein.

13 . The polymer of claim 12 , each of said ω-amino-fatty acid residues covalently linked to said at least two of said lysine residues is 8-amino-caprylic acid residue.

14 . The polymer of claim 1 , being selected from the group of compounds presented in Table 3.

15 . A pharmaceutical composition comprising, as an active ingredient, the polymer of claim 1 and a pharmaceutically acceptable carrier.

16 . The pharmaceutical composition of claim 15 , further comprising at least one additional therapeutically active agent.

17 . The pharmaceutical composition of claim 16 , wherein said at least one additional therapeutically active agent comprises an antibiotic agent.

18 . An imaging probe for detecting a pathogenic microorganism, the imaging probe comprising the polymer of claim 1 , said polymer further comprising at least one labeling agent attached thereto.

Assignees

• Technion Res & Dev Foundation

Inventors

• Mor Amram
• Radzishevsky Inna

Classifications

• C12Q1/04 Primary

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title

• C07K14/001

  by chemical synthesis · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61M15/00

  Inhalators {(drug delivery in endotracheal tubes A61M16/04)} · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title