ANTI-MICROBIAL TARGETING CHIMERIC PHARMACEUTICAL
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)