Novel antimicrobial agents

Abstract

A novel class of antimicrobial polymeric agents which are designed to exert antimicrobial activity while being stable, non-toxic and avoiding development of resistance thereto and a process of preparing same are disclosed. Further disclosed are pharmaceutical compositions containing same and a method of treating medical conditions associated with pathological microorganisms, a medical device, an imaging probe and a food preservative utilizing same. Further disclosed are conjugates of an amino acid residue and a hydrophobic moiety residue and a process of preparing same.

1 .- 81 . (canceled) 
     
     
         82 . A polymer comprising a plurality of positively charged amino acid residues and at least one ω-amino-fatty acid residue, wherein said ω-amino-fatty acid residue is being covalently linked to at least two amino acid residues in said plurality of positively charged amino acid residues via the N-alpha of one amino acid residue and via the C-alpha of the other amino acid residue in said at least two amino acid residues, said at least one ω-amino-fatty acid being linked to each of said amino acid residues via a peptide bond, the polymer having an antimicrobial activity. 
     
     
         83 . The polymer of  claim 82 , being capable of selectively destructing at least a portion of the cells of a pathogenic microorganism. 
     
     
         84 . The polymer of  claim 83 , wherein said pathogenic microorganism is selected from the group consisting of a prokaryotic organism, an eubacterium, an archaebacterium, a eukaryotic organism, a yeast, a fungus, an alga, a protozon and a parasite. 
     
     
         85 . The polymer of  claim 82 , comprising at least one fatty acid residue being linked via a peptide bond to the N-alpha of an amino acid residue at the N-terminus of said plurality of positively charged amino acid residues. 
     
     
         86 . The polymer of  claim 82 , further comprising at least one fatty acid residue being linked to the side-chain of an amino acid residue of said plurality of positively charged amino acid residues. 
     
     
         87 . The polymer of  claim 82 , wherein said plurality of amino acid residues comprises from 2 to 50 positively charged amino acid residues. 
     
     
         88 . The polymer of  claim 82 , wherein each of said positively charged amino acid residues is independently selected from the group consisting of a histidine residue, a lysine residue, an ornithine residue and an arginine residue. 
     
     
         89 . The polymer of  claim 82 , comprising from 1 to 50 ω-amino-fatty acid residues. 
     
     
         90 . The polymer of  claim 82 , wherein said hydrophobic moiety residue comprises at least one hydrocarbon chain. 
     
     
         91 . The polymer of  claim 82 , wherein said hydrophobic moiety residue comprises at least one fatty acid residue. 
     
     
         92 . The polymer of  claim 91 , wherein said at least one fatty acid residue is selected from the group consisting of an unbranched saturated fatty acid residue, a branched saturated fatty acid residue, an unbranched unsaturated fatty acid residue, a branched unsaturated fatty acid residue and any combination thereof. 
     
     
         93 . The polymer of  claim 91 , wherein said fatty acid residue is selected from the group consisting of a butyric acid residue, a caprylic acid residue and a lauric acid residue. 
     
     
         94 . The polymer of  claim 82 , wherein said ω-amino-fatty acid is selected from the group consisting of 4-amino-butyric acid, 6-amino-caproic acid, 8-amino-caprylic acid, 10-amino-capric acid, 12-amino-lauric acid, 14-amino-myristic acid, 16-amino-palmitic acid, 18-amino-stearic acid, 18-amino-oleic acid, 16-amino-palmitoleic acid, 18-amino-linoleic acid, 18-amino-linolenic acid and 20-amino-arachidonic acid. 
     
     
         95 . The polymer of  claim 94 , wherein said ω-amino-fatty acid is selected from the group consisting of 4-amino-butyric acid, 8-amino-caprylic acid and 12-amino-lauric acid. 
     
     
         96 . The polymer of  claim 82 , further comprising at least one active agent attached thereto. 
     
     
         97 . The polymer of  claim 96 , wherein said at least one active agent is a labeling agent. 
     
     
         98 . The polymer of  claim 97 , wherein said labeling agent is selected from the group consisting of a fluorescent agent, a radioactive agent, a magnetic agent, a chromophore, a phosphorescent agent and a heavy metal cluster. 
     
     
         99 . The polymer of  claim 96 , wherein said at least one active agent comprises at least one therapeutically active agent. 
     
     
         100 . The polymer of  claim 99 , wherein said at least one therapeutically active agent is selected from the group consisting of an agonist residue, an amino acid residue, an analgesic residue, an antagonist residue, an antibiotic agent residue, an antibody residue, an antidepressant agent, an antigen residue, an anti-histamine residue, an anti-hypertensive agent, an anti-inflammatory drug residue, an anti-metabolic agent residue, an antimicrobial agent residue, an antioxidant residue, an anti-proliferative drug residue, an antisense residue, a chemotherapeutic drug residue, a co-factor residue, a cytokine residue, a drug residue, an enzyme residue, a growth factor residue, a heparin residue, a hormone residue, an immunoglobulin residue, an inhibitor residue, a ligand residue, a nucleic acid residue, an oligonucleotide residue, a peptide residue, a phospholipid residue, a prostaglandin residue, a protein residue, a toxin residue, a vitamin residue and any combination thereof. 
     
     
         101 . The polymer of  claim 96 , being capable of delivering at least one active agent to at least a portion of the cells of a pathogenic microorganism. 
     
     
         102 . The polymer of  claim 101 , wherein said pathogenic microorganism is selected from the group consisting of a prokaryotic organism, an eubacterium, an archaebacterium, a eukaryotic organism, a yeast, a fungus, an alga, a protozon and a parasite. 
     
     
         103 . The polymer of  claim 101 , wherein said at least one active agent is a labeling agent. 
     
     
         104 . The polymer of  claim 101 , wherein said at least one active agent comprises at least one therapeutically active agent. 
     
     
         105 . A polymer having the general formula I:
   X—W 0 -[A 1 -Z 1 -D 1 ]-W 1 -[A 2 -Z 2 -D 2 ]-W 2 -[An-Zn-Dn]-Wn-Y   Formula I   wherein:   n is an integer from 2 to 50;   A 1 , A 2 , . . . , An are each independently a positively charged amino acid residue;   D 1 , D 2 , Dn are each independently a ω-amino-fatty acid residue or absent, provided that at least one of said D 1 , D 2 , . . . , Dn is said ω-amino-fatty acid residue;   Z 1 , Z 2 , Zn and W 0 , W 1 , W 2 , . . . , Wn are each a peptide bond linking an amino acid residue and a ω-amino-fatty acid residue, or absent;   X and Y are each independently selected from the group consisting of hydrogen, amine, amide, an amino acid residue, a fatty acid residue and an ω-amino-fatty acid residue.   
     
     
         106 . The polymer of  claim 105 , having an antimicrobial activity. 
     
     
         107 . The polymer of  claim 106 , being capable of selectively destructing at least a portion of the cells of a pathogenic microorganism. 
     
     
         108 . The polymer of  claim 107 , wherein said pathogenic microorganism is selected from the group consisting of a prokaryotic organism, an eubacterium, an archaebacterium, a eukaryotic organism, a yeast, a fungus, an alga, a protozon and a parasite. 
     
     
         109 . The polymer of  claim 105 , wherein each of said positively charged amino acid residues is independently selected from the group consisting of a histidine residue, a lysine residue, an ornithine residue and an arginine residue. 
     
     
         110 . The polymer of  claim 105 , wherein X is a fatty acid residue or an ω-amino-fatty acid residue. 
     
     
         111 . The polymer of  claim 105 , wherein Y is an ω-amino-fatty acid residue. 
     
     
         112 . The polymer of  claim 105 , wherein at least one of said amino acid residues has a fatty acid residue attached to a side chain thereof. 
     
     
         113 . The polymer of  claim 105 , wherein at least one of said hydrophobic moiety comprises at least one hydrocarbon chain. 
     
     
         114 . The polymer of  claim 105 , wherein at least one of said hydrophobic moiety comprises at least one fatty acid residue. 
     
     
         115 . The polymer of  claim 114 , wherein said at least one fatty acid residue is selected from the group consisting of a butyric acid residue, a caprylic acid residue and a lauric acid residue. 
     
     
         116 . The polymer of  claim 105 , wherein each of said ω-amino-fatty acid residues is independently selected from the group consisting of 4-amino-butyric acid, 6-amino-caproic acid, 8-amino-caprylic acid, 10-amino-capric acid, 12-amino-lauric acid, 14-amino-myristic acid, 16-amino-palmitic acid, 18-amino-stearic acid, 18-amino-oleic acid, 16-amino-palmitoleic acid, 18-amino-linoleic acid, 18-amino-linolenic acid and 20-amino-arachidonic acid. 
     
     
         117 . The polymer of  claim 105 , further comprising at least one active agent attached thereto. 
     
     
         118 . The polymer of  claim 117 , wherein said at least one active agent is a labeling agent. 
     
     
         119 . The polymer of  claim 117 , wherein said at least one active agent comprises at least one therapeutically active agent. 
     
     
         120 . A pharmaceutical composition comprising, as an active ingredient, the polymer of  claim 82  and a pharmaceutically acceptable carrier. 
     
     
         121 . The pharmaceutical composition of  claim 120 , being packaged in a packaging material and identified in print, in or on said packaging material, for use in the treatment of a medical condition associated with a pathogenic microorganism. 
     
     
         122 . The pharmaceutical composition of  claim 121 , wherein said pathogenic microorganism is selected from the group consisting of a prokaryotic organism, an eubacterium, an archaebacterium, a eukaryotic organism, a yeast, a fungus, an alga, a protozon and a parasite. 
     
     
         123 . The pharmaceutical composition of  claim 120 , further comprising at least one additional therapeutically active agent. 
     
     
         124 . The pharmaceutical composition of  claim 123 , wherein said at least one therapeutically active agent is selected from the group consisting of an agonist, an analgesic, an antagonist, an antibiotic agent, an antibody, an antidepressant, an antigen, an anti-histamine, an anti-hypertensive, an anti-inflammatory drug, an anti-metabolic agent, an antimicrobial agent, an antioxidant, an anti-proliferative agent, an antisense, a chemotherapeutic drug, a co-factor, a cytokine, an enzyme, a growth factor, a hormone, an immunoglobulin, an inhibitor, a ligand, a nucleic acid, an oligonucleotide, a prostaglandin, a toxin, a vitamin and any combination thereof. 
     
     
         125 . The pharmaceutical composition of  claim 123 , wherein said at least one additional therapeutically active agent comprises an antibiotic agent. 
     
     
         126 . A method of treating a medical condition associated with a pathogenic microorganism, the method comprising administering to a subject in need thereof a therapeutically effective amount of the polymer of  claim 82 . 
     
     
         127 . The method of  claim 126 , wherein said pathogenic microorganism is selected from the group consisting of a prokaryotic organism, an eubacterium, an archaebacterium, a eukaryotic organism, a yeast, a fungus, an alga, a protozon and a parasite. 
     
     
         128 . The method of  claim 126 , wherein said administering is effected orally, rectally, intravenously, topically, intranasally, intradermally, transdermally, subcutaneously, intramuscularly, intraperitoneally or by intrathecal catheter. 
     
     
         129 . The method of  claim 126 , further comprising administering to said subject at least one therapeutically active agent. 
     
     
         130 . The method of  claim 129 , wherein said at least one therapeutically active agent is selected from the group consisting of an agonist, an analgesic, an antagonist, an antibiotic agent, an antibody, an antidepressant, an antigen, an anti-histamine, an anti-hypertensive, an anti-inflammatory drug, an anti-metabolic agent, an antimicrobial agent, an antioxidant, an anti-proliferative agent, an antisense, a chemotherapeutic drug, a co-factor, a cytokine, an enzyme, a growth factor, a hormone, an immunoglobulin, an inhibitor, a ligand, a nucleic acid, an oligonucleotide, a prostaglandin, a toxin, a vitamin and any combination thereof. 
     
     
         131 . The method of  claim 129 , wherein said at least one therapeutically active agent comprises an antibiotic agent. 
     
     
         132 . The method of  claim 126 , wherein said polymer is administered either per se or as a part of a pharmaceutical composition, said pharmaceutical composition further comprises a pharmaceutically acceptable carrier. 
     
     
         133 . A medical device comprising the polymer of  claim 82  and a delivery system configured for delivering said polymer to a bodily site of a subject. 
     
     
         134 . The medical device of  claim 133 , wherein said polymer forms a part of a pharmaceutical composition, said pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
     
     
         135 . The medical device of  claim 133 , wherein said delivering is effected by inhalation. 
     
     
         136 . The medical device of  claim 133 , wherein said delivering is effected transdermally. 
     
     
         137 . The medical device of  claim 133 , wherein said delivering is effected topically. 
     
     
         138 . The medical device of  claim 133 , wherein said delivering is effected by implanting the medical device in a bodily organ. 
     
     
         139 . A food preservative comprising an effective amount of the polymer of  claim 82 . 
     
     
         140 . The food preservative of  claim 139 , further comprising an edible carrier. 
     
     
         141 . An imaging probe for detecting a pathogenic microorganism, the imaging probe comprising a polymer, said polymer includes a plurality of amino acid residues and at least one hydrophobic moiety residue, wherein at least one of said at least one hydrophobic moiety residue is being covalently linked to at least two amino acid residues in said plurality of amino acid residues via the N-alpha of one amino acid residue and via the C-alpha of the other amino acid residue in said at least two amino acid residues, whereas said polymer further includes at least one labeling agent attached thereto. 
     
     
         142 . The imaging probe of  claim 141 , wherein said at least one labeling agent is attached to a side chain of at least one amino acid residue of said plurality of amino acid residues in said polymer. 
     
     
         143 . The imaging probe of  claim 141 , wherein said at least one labeling agent is attached to the C-terminus and/or the N-terminus of said plurality of amino acid residues in said polymer. 
     
     
         144 . The imaging probe of  claim 141 , wherein said at least one labeling agent is attached to at least one of said at least one hydrophobic moiety residue in said polymer. 
     
     
         145 . The imaging probe of  claim 141 , wherein said at least one labeling agent is selected from the group consisting of a chromophore, a fluorescent agent, a phosphorescent agent, a heavy metal cluster and a radioactive agent.