ANTIMICROBIAL FUSION PEPTIDES
Antimicrobial peptides, compositions and methods are described that are useful for treating infectious disease, including those caused by drug resistant Gram-negative bacteria (e.g., Pseudomonas and Acinetobacter ) and parasite-caused disease such as malaria. The peptides include a modular kinocidin gamma-core connected directly, or through a short spacer, to a kinocidin C-terminal alpha-helix.
1 . An isolated peptide comprising:
(1) a first fragment consisting of the amino acid sequence of SEQ ID NO:2 (CPTAQLIATLKNGRKICLDLQ) or a first amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2; and
(2) a second fragment consisting of the amino acid sequence of SEQ ID NO:3 (ALYKKFKKKLLKSLKRLG) or a second amino acid sequence having at least 85% sequence identity to SEQ ID NO: 3,
wherein the first fragment and the second fragment are connected directly or connected through a spacer that is 10 amino acids or fewer in length, and
wherein the first fragment is at the N-terminal end of the second fragment.
2 . The isolated peptide of claim 1 , wherein the first fragment and the second fragment are connected directly.
3 . The isolated peptide of claim 1 , wherein the first fragment and the second fragment are connected through the spacer.
4 . The isolated peptide of claim 3 , wherein the spacer is 5 amino acids or fewer in length.
5 . The isolated peptide of claim 1 , comprising the amino acid sequence of SEQ ID NO:1 (CPTAQLIATLKNGRKICLDLQALYKKFKKKLLKSLKRLG).
6 . The isolated peptide of claim 1 , comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO:1.
7 . The isolated peptide of claim 1 , comprising an amino acid sequence having from one to five amino acid substitutions from SEQ ID NO:1.
8 . The isolated peptide of claim 1 , wherein the peptide is not longer than 100 amino acids in length.
9 . The isolated peptide of claim 8 , wherein the peptide is not longer than 75 amino acids in length.
10 . The isolated peptide of claim 8 , wherein the peptide is not longer than 50 amino acids in length.
11 . The isolated peptide of claim 1 , wherein the peptide has antimicrobial activity.
12 . A polynucleotide comprising a nuclei acid sequence encoding the peptide of claim 1 .
16 . A composition comprising the peptide of claim 1 and a pharmaceutically acceptable carrier.
17 . A method of treating an infection in a patient in need thereof, comprising administering to the patient an effective amount of the composition of claim 16 .
18 . The method of claim 17 , wherein the infection is caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) or multidrug-resistant Acinetobacter baumannii (MDRAB).
19 . The method of claim 17 , wherein the infection is caused by a parasite.
20 . The method of claim 19 , wherein the patient suffers from malaria.