Cationic antimicrobial peptides

Abstract

A method for treating an infection comprises administering a peptide in synergistic combination with an antibiotic, wherein the peptide comprises an amino acid sequence with a formula selected from the group consisting of: (a) B n1 -Z; (b) B n1 -Z-B n2 ; and (c) Z-B n1 wherein B is a basic amino acid residue; n1 and n2 are 1 to 6; and Z is a sequence of from about 7 to about 24 amino acid residues, said sequence having an average hydrophobicity value of at least 0.3 on the Liu-Deber scale.

1 - 21 . (canceled) 
     
     
         22 . A composition comprising a synergistic combination of an antibiotic and a peptide comprising an amino acid sequence with a formula selected from the group consisting of:
 (a) B n1 -Z;   (b) B n1 -Z-B n2 ; and   (c) Z-B n1      wherein B is a basic amino acid residue;   n1 and n2 are 1 to 6; and   Z is a sequence of from about 7 to about 24 amino acid residues, said sequence having an average hydrophobicity value of at least 0.3 on the Liu-Deber scale.   
     
     
         23 . The composition of  claim 22 , wherein the peptide is selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (a) 
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                   KKKKKKXXFXXWXXFXX-NH 2 ; 
                 
                     
                     
                 
                     
                   (b) 
                 
                     
                   (SEQ ID NO: 20) 
                 
                     
                   KKKKKKAXFAXWXAFXA-NH 2 ; 
                 
                     
                     
                 
                     
                   (c) 
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   KKKKKKAAFAAWAAFAA-NH 2 ; 
                 
                     
                     
                 
                     
                   (d) 
                 
                     
                   (SEQ ID NO: 4) 
                 
                     
                   KKAFAAAAAFAAWAAFAKKKK-NH 2 ; 
                 
                     
                     
                 
                     
                   (e) 
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   RRRAAFAAWAAFAARRR-NH 2 ; 
                 
                     
                     
                 
                     
                   (f) 
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   KKAAAAFAAFAAWFAAFAAAAKKKK-NH 2 ; 
                 
                     
                     
                 
                     
                   (g) 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   KKATALVGAASLTAWVGLASAKKKK-NH 2 . 
                 
                     
                     
                 
                     
                   (h) 
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   KKAFAAAAAFAAXAAFAKKKK-NH 2 ; 
                 
                     
                     
                 
                     
                   (i) 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   KKKKKAAAFAAXAAFA-NH 2 ; 
                 
                     
                     
                 
                     
                   (j) 
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   RRRAAAFAAXAAFARRR-NH 2 ; 
                 
                     
                     
                 
                     
                   (k) 
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   KKAAAAFAAFAAXFAAFAAAAKKKK-NH 2 ; 
                 
                     
                     
                 
                     
                   (l) 
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   KKATALVGAASLTAXVGLASAKKKK-NH 2 ; 
                 
                     
                     
                 
                     
                   (m) 
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   KKKKKKAAAFAAAAAFAAWAAFAAA-NH 2 ; 
                 
                     
                     
                 
                     
                   (n) 
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   KKKAAAFAAWAAFAKKK-NH 2 ; 
                 
                     
                     
                 
                     
                   (o) 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   RRRRRRAAFAAWAAFAA-NH 2 ; 
                 
                     
                     
                 
                     
                   (p) 
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   KKKKKKAAAAFWAAAAF-NH 2 ; 
                 
                     
                     
                 
                     
                   (q) 
                 
                     
                   (SEQ ID NO: 17) 
                 
                     
                   KKKKKKAAFAAFAAFAA-NH 2 ; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (r) 
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   KKKKKKAAWAAWAAWAA-NH 2 ; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein X is any hydrophobic amino acid of hydropathy value greater than or equal to alanine. 
       
     
     
         24 . The composition of  claim 23 , wherein the peptide is selected from the group consisting of KKKKKKXXFXXWXXFXX-NH 2 , wherein each X is independently A, L, G, or S (SEQ ID NO: 1): KKKKKKAXFAXWXAFXA-NH 2 , wherein each X is independently selected from A or L (SEQ ID NO:2); and KKKKKKAAFAAWAAFAA-NH 2  (SEQ ID NO:3). 
     
     
         25 . The composition of  claim 23 , wherein the amino acids in the peptide are D-amino acids, L-amino acids, or a combination thereof. 
     
     
         26 . The composition of  claim 23 , wherein the peptide is a stapled peptide. 
     
     
         27 . The composition of  claim 26 , wherein the stapled peptide is a helix stapled peptide. 
     
     
         28 . The composition of  claim 23 , wherein the antibiotic is selected from the group consisting, of aminoglycosides, fluoroquinolones, carbapenem beta-lactam antibiotics, and combinations thereof. 
     
     
         29 . The composition of  claim 28 , wherein the antibiotic is selected from tobramycin, ciprofloxacin, meropenem, and combinations thereof. 
     
     
         30 . The composition of  claim 23 , formulated as a toothpaste, mouthwash, topical skin product, contact lens cleaning or storage solution, parenteral or enteral composition, a cleaning solution, or a cleaning wipe. 
     
     
         31 . (canceled) 
     
     
         32 . A composition comprising KKKKKKAAFAAWAAFAA-NH 2  (SEQ ID NO:3) and an antibiotic selected from the group consisting of tobramycin, ciprofloxacin, and meropenem.