Dermaseptin-type and piscidin-type antimicrobial peptides

Patent metadata

Field	Value
Publication number	US-10221222-B2
Application number	US-201515114037-A
Country	US
Kind code	B2
Filing date	Jan 26, 2015
Priority date	Jan 24, 2014
Publication date	Mar 5, 2019
Grant date	Mar 5, 2019

Abstract

Antimicrobial agents, including antimicrobial peptides (AMPs) and uses thereof. Compositions and methods of using dermaseptin-type and piscidin-type antimicrobial peptides that demonstrate activity and improved therapeutic indices against microbial pathogens. The peptide compositions demonstrate the ability to not only maintain or improve antimicrobial activity against bacterial pathogens including Gram-negative microorganisms Acinetobacter baumannii and Pseudomonas aeruginosa , but also significantly decrease hemolytic activity against human red blood cells. Specificity determinants within the AMPS change selectivity from broad spectrum antimicrobial activity to AMPS with gram-negative selectivity.

First claim

What is claimed is:

1. An antimicrobial peptide (AMP) comprising the amino acid sequence ALWMTLKKKVLKAKAKALNAVLVGANA (SEQ ID NO:9)
or a pharmaceutically-acceptable salt thereof and wherein the AMP exhibits at least one activity selected from:
at least a 50-fold increased antimicrobial selectivity for Gram-negative bacteria over Gram-positive bacteria compared to the selectivity of peptide SEQ ID NO:1
at least a 30-fold increased antimicrobial selectivity for prokaryotic cells over eukaryotic cells compared to the selectivity of peptide SEQ ID NO:1,
at least a 10-fold increased antimicrobial selectivity for prokaryotic cells over eukaryotic cells compared to the selectivity of peptide SEQ ID NO:6,
at least a 15-fold decreased hemolysis of human red blood cells compared to hemolysis exhibited by peptide SEQ ID NO:1,
at least a 10-fold decreased hemolysis of human red blood cells compared to hemolysis exhibited by peptide SEQ ID NO:6, and,
is equally effective in inhibiting the propagation of antibiotic resistant prokaryote methicillin-resistant Staphylococcus aureus (MRSA) and antibiotic sensitive prokaryote methicillin-sensitive Staphylococcus aureus (MSSA).

2. The AMP of claim 1 , wherein the amino acid sequence of the AMP consists of the sequence of SEQ ID NO:9.

3. A pharmaceutical composition comprising the AMP of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3 , comprising a mono-phasic pharmaceutical composition suitable for parenteral or oral administration consisting essentially of a therapeutically-effective amount of at least one peptide of claim 1 , and a pharmaceutically acceptable carrier.

5. A method of treating a Gram-negative bacterial infection wherein the infecting microorganism is selected from the group consisting of Acinetobacter baumannii, Pseudomonas aeruginosa , multi-drug resistant Pseudomonas aeruginosa , and multi-drug resistant Acinetobacter baumannii , comprising administering to a subject in need thereof a therapeutically effective amount of the AMP of claim 1 .

6. The method of claim 5 , wherein the administration of the peptide or pharmaceutical composition is by an administration route selected from oral, topical, intravenous, intraperitoneal, intramuscular, intradermal, intrasternal, intraarticular injection, or infusion.

Assignees

• Univ Colorado Regents

Inventors

• Jiang Ziqing
• Hodges Robert S
• Gera Lajos
• Mant Colin T

Classifications

• C07K14/463 Primary

  from amphibians · CPC title

• A61K38/00

  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) · CPC title

• C07K14/461

  from fish · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title