Novel antimicrobial peptides with heparin binding activity

Abstract

The invention relates to an antimicrobial peptide with heparin binding activity, being derived from endogenous mammalian proteins being substantially free from antimicrobial activity selected from the group consisting of laminin isoforms, complement factor C3, histidin rich glycoprotein and kininogen and having from 10 to 36 amino acid residues, wherein the antimicrobial peptide consists of at least four amino acid residues selected from the group consisting of K, R and H. The invention also relates to pharmaceutical compositions comprising said antimicrobial peptide and use of the antimicrobial peptide and/or antimicrobial/pharmaceutical composition.

1 .- 49 . (canceled)  
     
     
         50 . An antimicrobial peptide with heparin binding activity, the peptide comprising a 10 to 36 amino acid residue portion of the amino acid sequence KHNLGHGHKH ERDQGHGHQR GHGLGHGHEQ QHGLGHGHKF KLDDDLEHQG GHVLDHGHKHKHGHGHGKH KNKGKKNGKH NGWK or a variant thereof, wherein at least 30% of the residues of the 10 to 36 amino acid residue portion are selected from the group consisting of K, R and H.  
     
     
         51 . The peptide of  claim 50 , wherein at least 40% of the residues of the 10 to 36 amino acid residue portion are selected from the group consisting of K, R and H.  
     
     
         52 . The peptide of  claim 50 , wherein at least 50% of the residues of the 10 to 36 amino acid residue portion are selected from the group consisting of K, R and H.  
     
     
         53 . The peptide of  claim 50 , wherein the 10 to 36 amino acid residue portion comprises at least 20% H amino acid residues.  
     
     
         54 . The peptide of  claim 50 , wherein the peptide consists of 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 amino acid residues.  
     
     
         55 . The peptide of  claim 50 , wherein the 10 to 36 amino acid residue portion is selected from the group consisting of SEQ ID NO 1, 2 and 3.  
     
     
         56 . The peptide of  claim 50 , wherein the 10 to 36 amino acid residue portion is endogenous, synthetic, or semisynthetic.  
     
     
         57 . The peptide of  claim 50 , wherein the peptide is linked to one or more other antimicrobial peptide(s) or other substances.  
     
     
         58 . The peptide of  claim 50 , wherein the peptide is extended by 1-100 amino acid residues at either the N- or C-terminal end, or at both ends.  
     
     
         59 . The peptide of  claim 58 , wherein the peptide is extended by 5-50 amino acid residues.  
     
     
         60 . The peptide of  claim 59 , wherein the peptide is extended by 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid residues.  
     
     
         61 . The peptide of  claim 50 , wherein the 10 to 36 amino acid residue portion is modified by substitution of one to six amino acids.  
     
     
         62 . The peptide of  claim 50 , wherein the peptide(s) are modified by amidation, esterification, acylation, acetylation, PEGylation or alkylation.  
     
     
         63 . A composition comprising the peptide according to  claim 50 , the composition comprising a pharmaceutically acceptable buffer, diluent, carrier, adjuvant or excipient.  
     
     
         64 . The composition of  claim 63 , wherein the composition comprises a salt.  
     
     
         65 . The composition of  claim 64 , wherein the salt is selected from the group consisting of monovalent sodium, potassium or divalent zinc, magnesium, copper and calcium.  
     
     
         66 . The composition of  claim 65 , wherein the cation in the salt is divalent zinc.  
     
     
         67 . The composition of  claim 63 , wherein the composition has a pH from about 5.0 to about 7.0.  
     
     
         68 . The peptide of  claim 50 , wherein the peptide is in the form of a composition comprising a mixture of between 1, 2, 3 or 4 different polypeptides.  
     
     
         69 . The composition of  claim 63 , additionally comprising one or more antibiotic and/or antiseptic agent(s).  
     
     
         70 . The composition of  claim 50 , in the form of granules, powders, tablets, coated tablets, capsules, suppositories, syrups, emulsions, gels, ointments, suspensions, creams, aerosols, droplets or injectable forms.  
     
     
         71 . A method of preventing, inhibiting, reducing, or destroying microorganisms selected from the group consisting of bacteria, viruses, parasites, fungus, and yeast, the method comprising administering to a patient the peptide of  claim 50 .  
     
     
         72 . The method of  claim 71 , wherein the patient has a microbial infection.  
     
     
         73 . The method of  claim 72 , wherein the microbial infection is caused by a microorganism selected from the group consisting of  Enterococcus faecalis, Eschericia coli, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus pneumoniae, Streptococcus pyogenes  and  Staphylococcus aureus.    
     
     
         74 . The method of  claim 72 , wherein the microbial infection is caused by a microorganism selected from the group consisting of  Candida albicans  of  Candida parapsilosis.    
     
     
         75 . The method of  claim 72 , wherein the patient is a mammal.  
     
     
         76 . The method of  claim 71 , wherein the peptide is administered in the form of a composition comprising a plaster, wound dressing, suture, or adhesive.  
     
     
         77 . An antimicrobial peptide with heparin binding activity, the peptide comprising a 10 to 36 amino acid residue portion of the amino acid sequence SVQLTEKRM DKVGKYPKEL RKCCEDGMRE NPMRFSCQRR TRFISLGEAC KKVFLDCCNY ITELRRQHAR ASHLGLAR or a variant there of, wherein the 10 to 36 amino acid residue portion comprises at least four amino acids selected from the group consisting of K, R and H.