Omega-alicyclic tunicamycins and analogs

Patent metadata

Field	Value
Publication number	US-12245589-B2
Application number	US-202217718981-A
Country	US
Kind code	B2
Filing date	Apr 12, 2022
Priority date	Apr 12, 2022
Publication date	Mar 11, 2025
Grant date	Mar 11, 2025

Abstract

The invention relates to new tunicamycin structures comprising N-acyl groups metabolically integrated into the terminus of the TUN via the Streptomyces branched chain fatty acid pathways and variants thereof, and methods of preparing such new tunicamycin structures. The invention further relates to antibacterial compositions comprising such new tunicamycin structures, and methods for using such antibacterial compositions for killing Gram-positive bacteria.

First claim

We claim:

1. An N-acyl-tunicamycin variant of

wherein n is independently any integer from 7 to 13; and
X is a tert-butyl-branched chain, a cyclopropane, a cyclobutane, a cyclopentane, a cyclohexane, a cycloheptane, an unsaturated cyclohexene, or an unsaturated cyclopentene.

2. An antibacterial composition comprising at least one N-acyl-tunicamycin variant of claim 1 .

3. The antibacterial composition of claim 2 , further comprising an antibiotic, wherein said antibiotic is a β-lactam antibiotic, a non-β-lactam antibiotic, or combination thereof.

4. A method of killing Gram-positive bacteria in or on an animal comprising administering to an animal in need thereof an effective amount of the antibacterial composition of claim 2 .

5. A method of killing Gram-positive bacteria in or on an animal comprising administering to an animal in need thereof an effective amount of the antibacterial composition of claim 3 .

6. A method of disinfecting an object or a surface that has Gram-positive bacteria, the method comprising applying an effective amount of the N-acyl-tunicamycin variant of claim 1 to the object or the surface in order to kill the Gram-positive bacteria present on the object or the surface.

7. A method for preparing an N-acyl-tunicamycin variant of claim 1 , the method comprising fermenting under aerobic conditions a tunicamycin (TUN)-producing Actinomycetes strain in liquid culture in the presence of small organic carboxylic acids.

8. The N-acyl-tunicamycin variant of claim 1 , wherein the N-acyl-tunicamycin variant has antibacterial activity and blocks mycobacterial biofilm formation, wherein the bacteria is Gram-positive.

9. An N-acyl-tunicamycin variant of formula 2

wherein n is independently any integer from 7 to 13; and
X is a tert-butyl-branched chain, a cyclopropane, a cyclobutane, a cyclopentane, a cyclohexane, a cycloheptane, an unsaturated cyclohexene, or an unsaturated cyclopentene.

10. The N-acyl-tunicamycin variant of claim 1 , wherein X is an unsaturated cyclohexene or cyclopentene.

Assignees

• Us Agriculture

Inventors

• Price Neil P
• Jackson Michael A
• Hartman Trina M
• Bannantine John P

Classifications

• A01P1/00

  Disinfectants; Antimicrobial compounds or mixtures thereof · CPC title

• C12P21/005

  Glycopeptides, glycoproteins · CPC title

• C12N1/20

  Bacteria; Culture media therefor · CPC title

• C12R2001/52

  Streptomyces chartreusis · CPC title

• C07H19/06 Primary

  Pyrimidine radicals · CPC title