title: Influence of metallocene substitution on the antibacterial activity of multivalent peptide conjugates.
abstract: Peptide dendrimers and derivatisation of peptides with metallocenes showed promising results in the search for new antibacterial agents. The two concepts are combined in this work leading to multivalent, metallocene-containing peptide derivates. These new peptides were synthesised utilising microwave assisted, copper(I) catalyzed alkyne-azide cycloaddition (CuAAC, "click" chemistry). Twelve new peptide conjugates, containing either a ferrocenoyl group or a ruthenocenoyl group on so-called ultrashort (i.e. < 5 amino acids) peptides, and ranging from monovalent to trivalent conjugates, were synthesised and their antibacterial activity was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains. The antibacterial activity was compared to the same peptide conjugates without metallocenes. The resulting MIC values showed a significant enhancement of the antibacterial activity of these peptide conjugates against Gram-positive bacteria by the metallocenoyl groups. Additionally, the compounds with two metallocenoyl groups presented the best antibacterial activities overall.
authors.affiliation: Inorganic Chemistry I - Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Hoffknecht
authors.affiliation: Faculty of Biology, Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Prochnow
authors.affiliation: Faculty of Biology, Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Bandow
authors.affiliation: Inorganic Chemistry I - Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany. Electronic address: nils.metzler-nolte@rub.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Metzler-Nolte
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000254:growth & development; D000480:Alkynes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001386:Azides / Q000737:chemistry; D001412:Bacillus subtilis / Q000187:drug effects / Q000254:growth & development; D057930:Click Chemistry; D061565:Cycloaddition Reaction; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005296:Ferrous Compounds / Q000737:chemistry; D000075163:Metallocenes; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D009942:Organometallic Compounds / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D000900:Anti-Bacterial Agents; D001386:Azides; D005296:Ferrous Compounds; D000075163:Metallocenes; D009842:Oligopeptides; D009942:Organometallic Compounds; C013108:metallocene; C016721:ruthenocene; C004998:ferrocene
keywords: Antimicrobial Peptides; Bioorganometallic Chemistry; Medicinal Inorganic Chemistry; Metallocenes; Metallodrugs; synthetic Antimicrobial Peptides (synAMP)