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 . A method of preventing and/or treating a fungal and/or protist infection in a subject in need of such prevention and/or treatment, comprising:
 providing a composition comprising a polypeptide, or a derivative or analogue thereof, comprising repeats of a peptide derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of an apolipoprotein; and   administering a therapeutically effective amount of said composition to said subject.   
     
     
         2 . The method of  claim 1 , wherein the peptide is derived from a HSPG receptor binding region of apolipoprotein B or apolipoprotein E. 
     
     
         3 . The method of  claim 1 , wherein the peptide is derived from an apolipoprotein B LDL receptor binding domain cluster B, or from an apolipoprotein E LDL receptor binding domain cluster B. 
     
     
         4 . The method of  claim 1 , wherein the polypeptide comprises at least two RKR motifs. 
     
     
         5 . The method of  claim 1 , wherein the polypeptide comprises a tandem dimer repeat of: SEQ ID No.5; SEQ ID No.6; SEQ ID No.7; or a derivative thereof wherein at least one amino acid residue, 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. 
     
     
         6 . The method of  claim 5 , wherein the replaced or substituted residue is the first, second, third, seventh, eighth, ninth, tenth, eleventh, twelfth, sixteenth, seventeenth or eighteenth residue of the polypeptide. 
     
     
         7 . The method of  claim 5 , wherein the at least one amino acid substitution is an Arginine (R), a Phenylalanine (F) or a Tryptophan (W) residue, or a derivative thereof. 
     
     
         8 . The method of  claim 1 , wherein the polypeptide has the formula:
   {abcRKRxyz}+{a′b′c′RKRx′y′z′}  (formula I)   wherein a and a′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); and Cysteine (C); or are deleted;   b and b′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); and Cysteine (C); or are deleted;   c and c′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Threnonine (T); and Cysteine (C); or are deleted;   x and x′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Glycine (G); and Cysteine (C); or are deleted;   y and y′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); and Cysteine (C); or are deleted;   z and z′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); and Cysteine (C); or are deleted.   
     
     
         9 . The method of  claim 8 , wherein the polypeptide comprises at least one additional amino acid, which is independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); and Histidine (H), and which additional amino acid is added before the amino acid at position ‘a’ in the peptide of formula I at the N-terminal. 
     
     
         10 . The method of  claim 1 , wherein the polypeptide comprises a repeat of the peptide apoE 141-149  (SEQ ID NO. 5) or a variant thereof. 
     
     
         11 . The method of  claim 10  wherein the tandem repeat comprises at least two substitutions independently selected from Tryptophan (W), Arginine (R), Lysine (K), Tyrosine (Y), and Phenylalanine (F) substitutions. 
     
     
         12 . The method of  claim 10 , wherein the polypeptide comprises the amino acid sequence as defined by any one of SEQ ID NOs. 8-34. 
     
     
         13 . The method  claim 1 , wherein the polypeptide comprises repeats of a peptide derived from an HSPG receptor binding region of apoB. 
     
     
         14 . The method of  claim 13 , wherein the polypeptide is derived from a human apolipoprotein B LDL receptor binding domain cluster B. 
     
     
         15 . The method of  claim 14 , wherein the polypeptide comprises a repeat of apoB 3359-3367  (SEQ ID No. 6) or a truncation or variant thereof. 
     
     
         16 . The method of  claim 13 , wherein the polypeptide comprises the amino acid sequence as defined by any one SEQ ID NOs. 36-55. 
     
     
         17 . The method of  claim 1 , wherein the infection is an  Ascomycete  infection. 
     
     
         18 . The method of  claim 1 , wherein the infection is an infection with a fungus independently selected from the group consisting of  Aspergillus  spp.;  Candida  spp.; and  Fusarium  spp. 
     
     
         19 . The method of  claim 1 , wherein the infection is a Sarcodina infection. 
     
     
         20 . The method of  claim 1 , wherein the infection an infection with  Plasmodium  spp. or  Acanthamoeba  spp. 
     
     
         21 . (canceled) 
     
     
         22 . A method of preventing and/or treating a fungal and/or protist contamination comprising
 providing a composition comprising a polypeptide, or a derivative or analogue thereof, comprising repeats of a peptide derived from a Heparan Sulphate Proteoglycan (HSPG) receptor binding region of an apolipoprotein; and   coating an object or a surface in need thereof with an amount of said composition to kill or prevent growth of fungi or protists.   
     
     
         23 . The method according to  claim 22 , wherein the object is selected from the group consisting of medical devices, lenses, contact lenses, catheters, stents, wound healing dressings, contraceptives, surgical implants and replacement joints. 
     
     
         24 . The method according to  claim 22 , wherein the surface is selected from the group consisting of hospital ward surfaces, operating theatre surfaces, kitchen surfaces and sanitary surfaces. 
     
     
         25 . The method of  claim 22 , wherein the peptide is derived from a HSPG receptor binding region of apolipoprotein B or apolipoprotein E. 
     
     
         26 . The method of  claim 22 , wherein the peptide is derived from an apolipoprotein B LDL receptor binding domain cluster B, or from an apolipoprotein E LDL receptor binding domain cluster B. 
     
     
         27 . The method of  claim 22 , wherein the polypeptide comprises at least two RKR motifs. 
     
     
         28 . The method of  claim 1 , wherein the polypeptide comprises a tandem dimer repeat of: SEQ ID No.5; SEQ ID No.6; SEQ ID No.7; or a derivative thereof wherein at least one amino acid residue, 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 of  claim 28 , wherein the replaced or substituted residue is the first, second, third, seventh, eighth, ninth, tenth, eleventh, twelfth, sixteenth, seventeenth or eighteenth residue of the polypeptide. 
     
     
         30 . The method of  claim 28 , wherein the at least one amino acid substitution is an Arginine (R), a Phenylalanine (F) or a Tryptophan (W) residue, or a derivative thereof. 
     
     
         31 . The method of  claim 22 , wherein the polypeptide has the formula:
   {abcRKRxyz}+{a′b′c′RKRx′y′z′}  (formula I)   wherein a and a′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); and Cysteine (C); or are deleted;   b and b′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); and Cysteine (C); or are deleted;   c and c′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Threnonine (T); and Cysteine (C); or are deleted;   x and x′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); Glycine (G); and Cysteine (C); or are deleted;   y and y′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); and Cysteine (C); or are deleted;   z and z′ are each independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); Histidine (H); and Cysteine (C); or are deleted.   
     
     
         32 . The method of  claim 31 , wherein the polypeptide comprises at least one additional amino acid, which is independently selected from Arginine (R); Tyrosine (Y); Methionine (M); Isoleucine (I); Phenylalanine (F); Tryptophan (W); Leucine (L); Lysine (K); and Histidine (H), and which additional amino acid is added before the amino acid at position ‘a’ in the peptide of formula I at the N-terminal. 
     
     
         33 . The method of  claim 22 , wherein the polypeptide comprises a repeat of the peptide apoE 141-149  (SEQ ID NO. 5) or a variant thereof. 
     
     
         34 . The method of  claim 33  wherein the tandem repeat comprises at least two substitutions independently selected from Tryptophan (W), Arginine (R), Lysine (K), Tyrosine (Y), and Phenylalanine (F) substitutions. 
     
     
         35 . The method of  claim 33 , wherein the polypeptide comprises the amino acid sequence as defined by any one of SEQ ID NOs. 8-34. 
     
     
         36 . The method of  claim 22 , wherein the polypeptide comprises repeats of a peptide derived from an HSPG receptor binding region of apoB. 
     
     
         37 . The method of  claim 36 , wherein the polypeptide is derived from a human apolipoprotein B LDL receptor binding domain cluster B. 
     
     
         38 . The method of  claim 36 , wherein the polypeptide comprises a repeat of apoB 3359-3367  (SEQ ID No. 6) or a truncation or variant thereof. 
     
     
         39 . The method of  claim 36 , wherein the polypeptide comprises the amino acid sequence as defined by any one SEQ ID NOs. 36-55. 
     
     
         40 . The method of  claim 22 , wherein the contamination is an  Ascomycete  contamination. 
     
     
         41 . The method of  claim 22 , wherein the contamination is with a fungus independently selected from the a group consisting of  Aspergillus  spp.;  Candida  spp.; and  Fusarium  spp. 
     
     
         42 . The method of  claim 22 , wherein the contamination is a Sarcodina contamination. 
     
     
         43 . The method of  claim 22 , wherein the contamination is with  Plasmodium  spp. or  Acanthamoeba  spp.