Treatment of fungal and/or protist infections

Abstract

The present invention relates to the use of a polypeptides, comprising repeats of a peptide derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of an apolipoprotein, for treating or preventing a fungal and/or protist infection. The invention further relates to the use of such peptides for treating or preventing the contamination of surfaces or objects with such peptides.

1 - 24 . (canceled) 
     
     
         25 . A method of preventing, reducing the likelihood, or treating a fungal or protist infection in a subject, comprising:
 administering to a subject in need of said prevention, reduction of likelihood or treatment an amount of a polypeptide that is effective for killing or preventing or reducing the likelihood of growth of fungi or protists; and   wherein the polypeptide comprises a 14-29 amino acid polypeptide derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of an apolipoprotein and comprises at least two RKR motifs.   
     
     
         26 . The method according to  claim 25 , wherein the polypeptide is derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of apolipoprotein B or apolipoprotein E. 
     
     
         27 . The method according to  claim 25 , wherein the polypeptide is derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of apolipoprotein B LDL receptor binding domain cluster B or apolipoprotein E LDL receptor binding domain cluster B. 
     
     
         28 . The method according to  claim 25 , wherein the polypeptide comprises a tandem dimer repeat of SEQ ID NO: 5; SEQ ID NO: 6; SEQ ID NO: 7; or derivatives thereof wherein at least one amino acid, other than RKR motifs, is replaced by an Arginine (R), Tyrosine (Y), Methionine (M), Isoleucine (I), Phenylalanine (F), Tryptophan (W), Cysteine (C) or a derivative thereof. 
     
     
         29 . The method according to  claim 25 , wherein at least one amino acid, other than RKR motifs, is replaced by an Arginine (R), Phenylalanine (F) or Tryptophan (W) or a derivative thereof. 
     
     
         30 . The method according to  claim 25 , wherein the polypeptide is of formula (I):
   abcRKRxyza′b′c′RKRx′y′z′  (I)
   
       wherein
 a & a′=is independently selected from Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Cysteine (C) or is deleted; 
 b & b′=is independently selected from Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Cysteine (C) or is deleted; 
 c & c′=is independently selected from Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Threonine (T); Cysteine (C); or is deleted; 
 x & x′=is independently selected from either Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Glycine (G); Cysteine (C) or is deleted; 
 y & y′=is independently selected from Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Cysteine (C) or is deleted; 
 z & z′=is independently selected from Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Cysteine (C) or is deleted; 
 
       wherein the polypeptide is 14-18 amino acids in length; and 
       wherein optionally an amino acid that is independently selected from Arginine (R): Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K)and Histidine (H) may be added before the amino acid at position “a”. 
     
     
         31 . The method according to  claim 25 , wherein the polypeptide comprises a repeat of apoE 141-149  (SEQ ID NO: 5) or a variant thereof. 
     
     
         32 . The method according to  claim 31 , wherein the polypeptide comprises at least two substitutions independently selected from Tryptophan (W); Arginine (R); Lysine (K); Tyrosine (Y) or Phenylalanine (F) substitutions. 
     
     
         33 . The method according to  claim 31 , wherein the polypeptide comprises the amino acid sequences as defined by any one of SEQ ID NOs: 8-34. 
     
     
         34 . The method according to  claim 25 , wherein the polypeptide comprises a repeat of apoB 3359-3367  (SEQ ID NO: 6) or a variant thereof. 
     
     
         35 . The method according to  claim 34 , wherein the polypeptide comprises the amino acid sequences as defined by any one of SEQ ID NOs: 36-55. 
     
     
         36 . The method according to  claim 25 , for preventing, reducing the likelihood, or treating a an Ascomycete fungal infection. 
     
     
         37 . The method according to  claim 25 , for preventing, reducing the likelihood, or treating an Onygenales fungal infection. 
     
     
         38 . The method according to  claim 37 , wherein the fungus is a  Epidermophyton  spp.,  Microsporum  spp. or  Trichophyton  spp. 
     
     
         39 . The method according to  claim 37 , wherein the fungus is a  Candida  spp 
     
     
         40 . The method according to  claim 25 , wherein the peptide is formulated for topical application. 
     
     
         41 . The method according to  claim 25 , wherein the polypeptide has an IC 50  of 75 μM or less. 
     
     
         42 . The method according to  claim 25 , wherein the polypeptide is used to prevent, reduce the likelihood, or treat athletes foot. 
     
     
         43 . A method of reducing the likelihood of, or treating a fungal or protist contamination of a non-living object or surface, comprising:
 applying to the object or surface an amount of a 14-29 amino acid polypeptide that is effective for killing or inhibiting growth of fungi or protists,   wherein the polypeptide is derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of an apolipoprotein.   
     
     
         44 . A composition, comprising:
 a polypeptide comprising a 14-29 amino acid polypeptide derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of an apolipoprotein and comprises at least two RKR motifs; and   a pharmaceutically acceptable carrier.