title: Synthesis of Tridecaptin-Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria.
abstract: A series of tridecaptin-antibiotic conjugates were synthesized and evaluated for in vitro and in vivo activity against Gram-negative bacteria. Covalently linking unacylated tridecaptin A1 (H-TriA1) to rifampicin, vancomycin, and erythromycin enhanced their activity in vitro but not by the same magnitude as coadministration of the peptide and these antibiotics. The antimicrobial activities of the conjugates were retained in vivo, with the H-TriA1-erythromycin conjugate proving a more effective treatment of Klebseilla pneumoniae infections in mice than erythromycin alone or in combination with H-TriA1.
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, T6G 2G2, Canada.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Cochrane
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota 58203-9037, United States.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota 58203-9037, United States.
authors.forename: Sisi
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota 58203-9037, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences , Grand Forks, North Dakota 58203-9037, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta, T6G 2G2, Canada.
authors.forename: John C
authors.initials: JC
authors.lastname: Vederas
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004357:Drug Synergism; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D012293:Rifampin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; C017770:tridecaptins; D004917:Erythromycin; D014640:Vancomycin; D012293:Rifampin