Targeted antimicrobial moieties
This invention provides novel targeted antimicrobial compositions. In various embodiments chimeric moieties are provided comprising an antimicrobial peptide attached to a peptide targeting moiety that binds a bacterial strain or species.
1. A chimeric construct, said construct comprising:
a targeting peptide comprising the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554), where said targeting peptide is attached to an antimicrobial peptide, wherein said targeting peptide is attached to said antimicrobial peptide directly or through a peptide linker and where said chimeric construct is a fusion protein.
2. The chimeric construct of claim 1 , wherein said antimicrobial peptide comprises an amino acid sequence found in Table 4, and/or Table 5, and/or Table 14, and/or Table 15.
3. The chimeric construct of claim 1 , wherein said targeting peptide is linked directly to said antimicrobial peptide.
4. The chimeric construct of claim 1 , wherein said targeting peptide is linked to said antimicrobial peptide via a peptide linker.
5. The chimeric construct of claim 4 , wherein said targeting peptide is attached to said antimicrobial peptide by a peptide linker comprising an amino acid sequence selected from the group consisting of AAA, GGG, GGGG (SEQ ID NO:3212), SGG, GGSGGS (SEQ ID NO:3213), SAT, PYP, PSPSP (SEQ ID NO:3216), ASA, ASASA (SEQ ID NO:3215), KKKK (SEQ ID NO:3217), RRRR (SEQ ID NO:3218), GGGGS (SEQ ID NO:3219), GGGGS GGGGS (SEQ ID NO:3220), GGGGS GGGGS GGGGS (SEQ ID NO:3221), GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3222), GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3223), and GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3224).
6. A pharmaceutical composition comprising a chimeric construct of claim 1 in a pharmaceutically acceptable carrier.
7. A composition comprising a targeting peptide comprising the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554), where said targeting peptide is attached to a photosensitizing agent, wherein said photosensitizing agent is selected from the group consisting of a porphyrin, a cyanine, and a phthalocyanine.
8. The chimeric construct of claim 1 , wherein said antimicrobial peptide comprises an antimicrobial peptide selected from the group consisting of FLKFLKKFFKKLKY (SEQ ID NO:1044), KLFKFLRKHLL (SEQ ID NO:1034), and KNLRIIRKGIHIIKKY (SEQ ID NO:3082).
9. The chimeric construct of claim 1 , wherein said construct bears one or more protecting groups.
10. The chimeric construct according to claim 9 , wherein said one or more protecting groups are independently selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, Tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and Trifluoroacetyl (TFA).
11. The chimeric construct of claim 9 , wherein said construct comprises a protecting group at a carboxyl and/or amino terminus.
12. The chimeric construct of claim 11 , wherein a carboxyl terminus is amidated.
13. The chimeric construct of claim 4 , wherein said targeting peptide is attached to said antimicrobial peptide by a peptide linker consisting of an amino acid sequence selected the group consisting of AAA, GGG, GGGG (SEQ ID NO:3212), SGG, GGSGGS (SEQ ID NO:3213), SAT, PYP, PSPSP (SEQ ID NO:3216), ASA, ASASA (SEQ ID NO:3215), KKKK (SEQ ID NO:3217), RRRR (SEQ ID NO:3218), GGGGS (SEQ ID NO:3219), GGGGS GGGGS (SEQ ID NO:3220), GGGGS GGGGS GGGGS (SEQ ID NO:3221), GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3222), GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3223), and GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3224).
14. The chimeric construct of claim 1 , wherein said targeting peptide ranges in length up to about 50 amino acids.
15. The chimeric construct of claim 1 , wherein the amino acid sequence of said targeting peptide consists of the sequence LATKLKYEKEHKKM (SEQ ID NO:554).