Antimicrobial cationic peptides
A novel class of cationic peptides having antimicrobial activity is disclosed. These peptides can be encompassed by the formulas: X 1 X 1 PX 2 X 3 X 2 P(X 2 X 2 P) n X 2 X 3 (X 5 ) 0 ; (SEQ ID NO:23) X 1 X 1 PX 2 X 3 X 4 (X 5 ) r PX 2 X 3 X 3 ; (SEQ ID NO:24) X 1 X 1 X 3 (PW) u X 3 X 2 X 5 X 2 X 2 X 5 X 2 (X 5 ) 0 ; and (SEQ ID NO:25) X 1 X 1 X 3 X 3 X 2 P(X 2 X 2 P) n X 2 (X 5 ) m ; (SEQ ID NO:26) wherein: m is 1 to 5; n is 1 or 2; o is 2 to 5; r is 0 to 8; u is 0 or 1; X 1 is Isoleucine, Leucine, Valine, Phenylalanine, Tyrosine, Tryptophan or Methionine; X 2 represents Tryptophan or Phenylalanine X 3 represents Arginine or Lysine; X 4 represents Tryptophan or Lysine; and X 5 represents Phenylalanine, Tryptophan, Arginine, Lysine, or Proline. The invention also provides a method of producing a cationic peptide variant having antimicrobial activity.
1. A method of inhibiting the growth of a Gram positive bacterium, a Gram negative bacterium, or a yeast comprising contacting the bacterium or the yeast with an inhibiting effective amount of an isolated peptide selected from the group consisting of:
ILKKWPWWPWRRK
(SEQ ID NO:1);
ILKPWKWPWWPWRRKK
(SEQ ID NO:2);
ILKPWKWPWWPWRR
(SEQ ID NO:3);
ILPWKKWPWWRWRR
(SEQ ID NO:4);
ILKKWPWWPWRR
(SEQ ID NO:5);
ILPWKWPWWPWRKWR
(SEQ ID NO:6);
ILPWKWPWWPWRRWR
(SEQ ID NO:7);
ILPWKWPWRR
(SEQ ID NO:10);
ILPWKWPWWPWWPWRR
(SEQ ID NO:11);
ILPWKWPWWPWWKKPWRR
(SEQ ID NO:12);
ILKKWPWWPWKWKK
(SEQ ID NO:18);
IKWPWYVWL
(SEQ ID NO:20);
ILPWKWFFPPWPWRR
(SEQ ID NO:21);
ILPWKWPPWPPWPWRR
(SEQ ID NO:22);
ILKKFPFFPPRRK
(SEQ ID NO:28); and
FFKKFPFFPFRRK
(SEQ ID NO:36).
2. The method of claim 1 , wherein the method inhibits the growth of the Gram positive bacterium.
3. The method of claim 2 , wherein the Gram positive bacterium is Staphylococcus aureus or Staphylococcus epidermidis.
4. The method of claim 1 , wherein the method inhibits the growth of the Gram negative bacterium.
5. The method of claim 4 , wherein the Gram negative bacterium is selected from the group consisting of E. coli, P. aeruginosa , and S. typhimurium.
6. The method of claim 1 , further comprising contacting the bacterium or the yeast with at least one antibiotic.
7. The method of claim 6 , wherein the antibiotic is selected from the group consisting of a β-lactam, novobiocin, and polymyxin B.
8. The method of claim 1 , wherein the yeast is Candida albicans.
9. The method of claim 1 , wherein the isolated peptide is C-terminally amidated or C-terminally methyl-esterified.
10. The method of claim 1 , wherein the N-terminal amino acid of said SEQ ID NO: 1 is synthesized in D-form.