Anti-microbial targeting chimeric pharmaceutical

Abstract

The present invention is based on the discovery of a composition that provides targeted anti-microbial effect. Specifically the composition contains a targeting moiety which recognizes a target microbial organism and an anti-microbial peptide moiety which has anti-microbial activity. In addition, the present invention provides methods of treating a microbial infection, e.g., on mucosal surfaces by using the compositions provided by the present invention.

1 . A composition useful for treatment of microbial organisms comprising a targeting moiety and
 an anti-microbial peptide moiety,   wherein the targeting moiety is coupled to the anti-microbial peptide moiety and recognizes a target microbial organism and wherein the composition has an anti-microbial effect on the target microbial organism.   
     
     
         2 . The composition of  claim 1 , wherein the targeting moiety is a peptide. 
     
     
         3 . The composition of  claim 1 , wherein the targeting moiety is a peptide having an amino acid sequence as shown in SEQ ID NO. 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, or 61. 
     
     
         4 . The composition of  claim 1 , wherein the targeting moiety is a peptide having an amino acid sequence as shown in SEQ ID NO. 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 and wherein the target microbial organism is  Pseudomonas.    
     
     
         5 . The composition of  claim 1 , wherein the target microbial organism is  P. aeroginosa.    
     
     
         6 . The composition of  claim 1 , wherein the targeting moiety is a peptide having an amino acid sequence as shown in SEQ ID NO. 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51 and wherein the target microbial organism is  Staphylococcus.    
     
     
         7 . The composition of  claim 6 , wherein the target microbial organism is  S. aureus.    
     
     
         8 . The composition of  claim 1 , wherein the targeting moiety is a peptide having an amino acid sequence as shown in SEQ ID NO. 52, 53, 54, 55, 56, 57, 58, 59, or 60 and wherein the target microbial organism is  E. coli.    
     
     
         9 . The composition of  claim 8 , wherein the target microbial organism is  E. coli  DH5α. 
     
     
         10 .- 17 . (canceled) 
     
     
         18 . The composition of  claim 2 , wherein the targeting moiety is coupled to the anti-microbial peptide moiety via a peptide linker. 
     
     
         19 . The composition of  claim 1 , wherein the anti-microbial peptide moiety comprises a peptide selected from the group consisting of alexomycin, andropin, apidaecin, bacteriocin, β-pleated sheet bacteriocin, bactenecin, buforin, cathelicidin, α-helical clavanin, cecropin, dodecapeptide, defensin, β-defensin, α-defensin, gaegurin, histatin, indolicidin, magainin, nisin, protegrin, ranalexin, and tachyplesin. 
     
     
         20 . The composition of  claim 1 , wherein the anti-microbial peptide moiety comprises a peptide selected from the group consisting of histatin 5, dhvarl, protegrin PG-1, and novispirin G10. 
     
     
         21 . The composition of  claim 1 , wherein the target microbial organism is selected from the group consisting of bacteria, ricketsia, fungi, yeasts, protozoa, and parasites. 
     
     
         22 . The composition of  claim 1 , wherein the target microbial organism is a cariogenic organism. 
     
     
         23 . The composition of  claim 1 , wherein the target microbial organism is  Streptococcus mutans.    
     
     
         24 . The composition of  claim 1 , wherein the target microbial organism is selected from the group consisting of  Escherichia coli, Shigella dysenteriae, Salmonella typhimurium, Streptococcus pneumoniae, Staphylococcus aureus , and  Pseudomonas aeruginosa.    
     
     
         25 . The composition of  claim 24 , wherein the anti-microbial peptide moiety comprises a peptide selected from the group consisting of buforin, cecropin, indolicidin, and nisin. 
     
     
         26 . The composition of  claim 1 , wherein the target microbial organism is selected from the group consisting of  Escherichia coli, Shigella dysenteriae, Salmonella typhimurium, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Cryptococcus neoformans, Candida krusei , and  Helicobacter pylori.    
     
     
         27 . The composition of  claim 26 , wherein the anti-microbial peptide moiety comprises a peptide selected from the group consisting of magainin and renalexin. 
     
     
         28 . A method of treating a target microbial organism infection comprising administering to a subject in need of such treatment an effective amount of the composition of  claim 1 . 
     
     
         29 . The method of  claim 28 , wherein the target microbial organism infection is on a mucosal surface. 
     
     
         30 . The method of  claim 28 , wherein the target microbial organism infection is on a surface containing biofilm. 
     
     
         31 . The method of  claim 29 , wherein the mucosal surface is selected from the group consisting of mouth, vagina, gastrointestinal tract, and esophageal tract. 
     
     
         32 . The method of  claim 28 , wherein the target microbial organism infection is a  S. mutans  infection in a mouth. 
     
     
         33 . The method of  claim 28 , wherein the target microbial organism infection is a  Candida albicans  infection in vagina. 
     
     
         34 . The method of  claim 28 , wherein the target microbial organism infection is an infection in gastrointestinal tract selected from the group consisting of a  Helicobacter pylori  infection,  Campylobacter jerjuni  infection,  Vibrio cholerae  infection,  salmonella  infection,  Shigella  infection, and  Escherichia coli  infection. 
     
     
         35 . The method of  claim 28 , wherein the target microbial organism infection is an oral infection selected from the group consisting of  porphyromonas gingivalis, Actinomyces, Veillonella  spirochetes, and gram-negative flora infection. 
     
     
         36 . The method of  claim 28 , wherein the target microbial organism infection is an  Clostridium difficile  infection in gastrointestinal tract or esophageal tract. 
     
     
         37 .- 46 . (canceled)