title: Mitogenic activity and the induction of tumor necrosis factor by lipopeptide analogs of the N-terminal part of lipoprotein in the outer membrane of Escherichia coli.
abstract: Mitogenicity and the production of tumor necrosis factor (TNF) by a chemically synthesized lipotetrapeptide analog (KAB-8), S-[2,3-bis(palmitoyloxy)-2R-propyl]-N-[(2,2,2)-trichloro- ethoxycarbonyl: Troc group]-(R)-cysteinyl-(S)-seryl-(S)-seryl-(S)-asparagine, the amino acid sequence of which corresponds to that of the lipopeptide part of lipoprotein in Escherichia coli, and several derivatives (KAB-30-41), which possessed the altered glycerocysteine moiety, were examined. A 1-cysteinyl glycerol skeleton-type compound (KAB-8), a propane-type compound (KAB-31), a homoglycerol-type (KAB-39 and 40) and a 2-cysteinyl glycerol-type (KAB-41) exhibited mitogenic activity on splenocytes from C3H/He mice at various concentrations ranging from 0.4 to 100 micrograms/ml. However, propane-type compounds, except KAB-31, and ethane-type compounds showed lower mitogenic activity than other types of compounds. Compounds KAB-8, 31, 40 and 41 induced the production of TNF in peritoneal exudated macrophages from C3H/He mice at concentrations of 25 and 50 micrograms/ml. The results indicate that the structural differences of the glycerol moiety in the synthetic lipopeptides affect the potency of its biological activities.
authors.affiliation: University of Shizuoka, School of Pharmaceutical Sciences, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagihara
authors.forename: M
authors.initials: M
authors.lastname: Kurimura
authors.forename: K
authors.initials: K
authors.lastname: Achiwa
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D004926:Escherichia coli / Q000737:chemistry*; D008074:Lipoproteins / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D008074:Lipoproteins; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha