Anti-fungal peptides

Abstract

The present invention relates generally to anti-fungal peptides derived from or based on Domain III (amino acids 142 - 169 ) of bactericidal/permeability-increasing protein (BPI) and therapeutic uses of such peptides.

What is claimed is:  
     
         1 . An antifungal peptide having from seven to twelve amino acids comprising: 
 (a) a core sequence of amino acids selected from the group consisting of LIQL, IQLF, WLIQL, LIQLF and WLIQLF; and    (b) one or more cationic amino acids selected from the group consisting of K, R, H, ornithine and diaminobutyric acid at the amino and/or carboxy terminal portion of the core sequence.    
     
     
         2 . An antifungal peptide having from seven to nine amino acids comprising: 
 (a) a core sequence of amino acids selected from the group consisting of LIQL and IQLF; and    (b) at least two cationic amino acids selected from the group consisting of K, R, H, ornithine and diaminobutyric acid at the amino and/or carboxy terminal portion of the core sequence.    
     
     
         3 . An antifungal peptide having from eight to ten amino acids comprising: 
 (a) a core sequence of amino acids selected from the group consisting of LIQLF and WLIQLF; and    (b) at least two cationic amino acids selected from the group consisting of K, R, H, ornithine and diaminobutyric acid at the amino and/or carboxy terminal portion of the core sequence.    
     
     
         4 . An antifungal peptide having from nine to twelve amino acids comprising: 
 (a) a core sequence of amino acids selected from the group consisting of WLIQLF; and    (b) at least three cationic amino acids selected from the group consisting of K, R, H, ornithine and diaminobutyric acid at the amino and/or carboxy terminal portion of the core sequence.    
     
     
         5 . An antifungal peptide according to  claim 1 ,  2 ,  3  or  4  selected from the group consisting of the peptides of SEQ ID NOS: 118-137 (XMP.285-304), 140-144 (XMP.307-311), 155-160 (XMP.322-327), 166-170 (XMP.335-339), 174-177 (XMP.343-346), 179-184 (XMP.348-353), 186 (XMP.355) and 188-190 (XMP.357-359).  
     
     
         6 . An antifungal peptide according to  claim 1 ,  2 ,  3  or  4  having one or more D-isomer amino acids.  
     
     
         7 . An antifungal peptide according to  claim 6  selected from the group consisting of the peptides of SEQ ID NOS: 164 (XMP.333), 165 (XMP.334), 173 (XMP.342), 194 (XMP.363) and 196 (XMP.365).  
     
     
         8 . An antifungal peptide according to  claim 6  wherein said core sequence amino acids comprise D-isomer amino acids in reverse sequence order.  
     
     
         9 . An antifungal peptide according to  claim 8  having the amino acid sequence set out in SEQ ID NOS: 163 (XMP.332) and 198 (XMP.367).  
     
     
         10 . An antifungal peptide according to  claim 1 ,  2 ,  3  or  4  wherein the amino terminal amino acid residue is acetylated.  
     
     
         11 . An antifungal peptide according to  claim 10  selected from the group consisting of the peptides of SEQ ID NOS: 162 (XMP.331), 185 (XMP.354), 187 (XMP.356), 195 (XMP.364), 199 (XMP.368) and 204 (XMP.373).  
     
     
         12 . A cyclic antifungal peptide according to  claim 1 ,  3  or  4 .  
     
     
         13 . A cyclic antifungal peptide according to  claim 3  selected from the group consisting of SEQ ID NOS: 191-193 (XMP.360-362).  
     
     
         14 . An antifungal peptide selected from the group consisting of peptides of SEQ ID NOS: 1 (XMP.5), 2-4 (XMP.11-13), 5 (XMP.29), 20 (XMP.55), 56 (XMP.137), 79 (XMP.235), 111-115 (XMP.271-275), 117 (XMP.284), 132 (XMP.299), 138-139 (XMP.305-306), 145-154 (XMP.312-321), 200-203 (XMP.369-372), BPI residues 145-159 and 149-163 of SEQ ID NO: 206 and 171-172 (XMP.340-341).  
     
     
         15 . A pharmaceutical composition comprising an antifungal peptide according to any of claims  1  through  14  and a pharmaceutically acceptable diluent, adjuvant or carrier.  
     
     
         16 . An in vitro method for killing or inhibiting replication of fungi comprising contacting the fungi with an antifungal peptide according to any one of claims  1  through  14 .  
     
     
         17 . A method of treating fungal infections comprising administering to a subject suffering from a fungal infection a therapeutically effective amount of a peptide according to any of claims  1  through  14 .  
     
     
         18 . A method according to  claim 17  wherein the fungal infection involves a fungal species selected from the group consisting of  Candida, Aspergillus  and  Cryptococcus species.    
     
     
         19 . A method according to  claim 18  wherein the Candida species is selected from the group consisting of  C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis  and  C. tropicalis.    
     
     
         20 . A method according to  claim 18  wherein the peptide is administered topically, intravenously, orally or as an aerosol.  
     
     
         21 . A method according to  claim 17  comprising the additional step of administering a non-peptide anti-fungal agent.