title: Identification and biological activity of ogipeptins, novel LPS inhibitors produced by marine bacterium.
abstract: A library of secondary metabolites from microorganisms was screened to identify novel inhibitors against lipopolysaccharide (LPS), a strong stimulant of innate immunity. Novel cyclic peptides, ogipeptin A, B, C and D, were identified in the culture broth of the marine bacterium Pseudoalteromonas sp. SANK 71903. These compounds blocked LPS binding to the cluster of differentiation 14 (CD14) in vitro with IC50values of 4.8, 6.0, 4.1 and 5.6 nm, respectively, and attenuated tumor necrosis factor-α secretion from LPS-stimulated macrophage-like cells. These compounds also displayed antimicrobial activity against Escherichia coli with minimum inhibitory concentrations ranging from 0.25 μg ml-1to 1 μg ml-1. Thus, novel antibiotics that inhibited LPS-induced innate immune reactions were identified in this study.
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Kozuma
authors.affiliation: Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota-Takahata
authors.affiliation: Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukuda
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Nahoki
authors.initials: N
authors.lastname: Kuraya
authors.affiliation: Organic Synthesis Department, Daiichi Sankyo RD Novare Co., Ltd., Tokyo, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ando
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D031161:Pseudoalteromonas / Q000378:metabolism*; D064210:Secondary Metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha