Synthesis, inhibitory effects on nitric oxide and structure-activity relationships of a glycosphingolipid from the marine sponge Aplysinella rhax and its analogues.
The novel glycosphingolipid, β-D-GalNAcp(1-->4)[α-D-Fucp(1-->3)]-β-D-GlcNAcp(1-->)Cer (A), isolated from the marine sponge Aplysinella rhax has a unique structure, with D-fucose and N-acetyl-D-galactosamine moieties attached to a reducing-end N-acetyl-D-glucosamine through an α1-->3 and β1-->4 linkage, respectively. We synthesized glycolipid 1 and some non-natural di- and trisaccharide analogues 2-6 containing a D-fucose residue. Among these compounds, the natural type showed the most potent nitric oxide (NO) production inhibitory activity against LPS-induced J774.1 cells. Our results indicate that both the presence of a D-Fucα1-3GlcNAc-linkage and the ceramide aglycon portion are crucial for optimal NO inhibition.
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Yuzo
Y
Fujita
Naohiro
N
Ohshima
Ai
A
Hasegawa
Frank
F
Schweizer
Tadahiro
T
Takeda
Fumiyuki
F
Kiuchi
Noriyasu
N
Hada
D000818:Animals; D002240:Carbohydrate Sequence; D002460:Cell Line; D006028:Glycosphingolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008386:Marine Biology; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011161:Porifera / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship
D006028:Glycosphingolipids; D009569:Nitric Oxide
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