Antimicrobial peptides, pharmaceutical compositions, and methods of use thereof
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsJie Zheng, Ann Marie Knolhoff, Eric Wayne Brown, Timothy Ray Croley
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Abstract
Disclosed herein are novel antimicrobial peptides, pharmaceutical compositions containing the peptides, and methods of use of the peptides to inhibit the growth or proliferation of microbes. The antimicrobial peptides are particularly useful to treat infections of dangerous gram positive organisms such as MRSA and VRSA.
Claims29
A method of inhibiting growth or proliferation of a bacterium, comprising contacting the bacterium with an effective amount of a peptide comprising the amino acid sequence:
- Xaa1-Val2-Thr3-D-Orn4-Ser5-Xaa6-Xaa7-D-Ser8-Ile9-Pro10-Ile11-Pro12-Ile13,
- wherein Xaa6 is Tyr or Phe, wherein Xaa1 and Xaa7 are each independently L-Lys D-Lys or D-Orn,
- and wherein the peptide optionally comprises a saturated or unsaturated, substituted or unsubstituted, linear or branched, C4-C20 fatty acid group, or a saturated or unsaturated, linear or branched C4-C20 ester covalently linked to Xaa1,
- thereby inhibiting the growth or proliferation of the bacterium.
A method of inhibiting growth or proliferation of a bacterium in a subject in need thereof, the method comprising administering to the subject a composition comprising a peptide and a pharmaceutically acceptable carrier, wherein the peptide comprises the amino acid sequence:
- Xaa1-Val2-Thr3-D-Orn4-Ser5-Xaa6-Xaa7-D-Ser8-Ile9-Pro10-Ile11-Pro12-Ile13,
- wherein Xaa6 is Tyr or Phe, wherein Xaa1 and Xaa7 are each independently L-Lys, D-Lys or D-Orn,
- wherein the peptide optionally comprises a saturated or unsaturated, substituted or unsubstituted, linear or branched, C4-C20 fatty acid group, or a saturated or unsaturated, linear or branched C4-C20 ester covalently linked to Xaa1,
- and wherein the composition is administered in an amount effective to inhibit growth or proliferation of the bacterium.
A method of inhibiting growth or proliferation of a Gram positive bacterium in a subject in need thereof, the method comprising contacting the bacterium with an effective amount of a peptide comprising the amino acid sequence D-Orn1-Val2-Thr3-D-Orn4-Ser5-Tyr6-Lys7-D-Ser8-Ile9-Pro10-Ile11-Pro12-Ile13, wherein the peptide is covalently linked to C13H25O, thereby inhibiting the growth or proliferation of the bacterium.
Dependencies are inferred from the claim text.