Natori (Japan)

Type: City
Name: Natori (Japan)
Country: Japan
Latitude: 38.16
Longitude: 140.880005
population: 75,563
First reported Aug 21 2014 - Updated Aug 21 2014 - 1 reports

"One-Pot Synthesis of Alpha/Beta-O-Clycolipids" in Patent Application Approval Process

By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- A patent application by the inventors Gervay-Hague, Jacquelyn ( Davis, CA ); Du, Wenjun ( Mount Pleasant, MI ); Kulkarni, Suvarn S. (Mumbai, IN); Schombs, Matthew ( Davis, CA ... [Published 4 Traders - Aug 21 2014]

Quotes

The following quote was obtained by the news editors from the background information supplied by the inventors: "In 1993, six novel galactosyl ceramides with unique .alpha.-glycosidic linkages were isolated from the marine sponge Agelas mauritianus near Okinawa, Japan . ( Natori , T et al., Tetrahedron Lett., 34, 5591 (1993); Natori , T et al., Tetrahedron, 50, 2771 (1994).) These compounds showed highly potent anti-tumor activities, which prompted various synthetic studies. (Motoki, K et al., Bioorg. Med. Chem. Lett., 5, 705 (1995).) Among the many analogues synthesized, KRN7000 (see structure below) was found to be the most potent (Kobayashi, E et al., Bio. Med. Chem., 4, 615 (1996)) and extensive mechanistic studies indicated that the anti-tumor activity was the result of CD1d-dependent natural killer T-cell (NKT) stimulation. (Kobayashi, E et al., Bio. Med. Chem., 4, 615 (1996); Kawano , T et al., Science, 278, 1626 (1997).) CD1d molecule is a member of the CD1 family proteins that present lipid antigens to NKT cells to activate the immune response. It is proposed that CD1d recognizes KRN7000 and the binding complex interacts with the T-cell receptor (TCR) to NKT cells stimulating the release of two major cytokines known as INF-.gamma. and IL-4. (Wu, D et al., Proc. Natl. Acad. Sci., 102, 1351 (2005); Porcelli, S A and Modlin R L , Annu. Rev. Immunol, 17, 297 (1999); Kinjo, Y et al., Nature, 434, 520 (2005).) The two cytokines, however, can cancel each other's beneficial therapeutic effect as one pathway down-regulates the other. (Pal, E et al., J Immunol., 166, 662 (2001); Berkers, C R and Ovaa, H , Trends. Pharmacol. Sci., 26, 252 (2005).) Interestingly, different KRN7000 analogs selectively stimulate cytokine production. For example, OCH (see structure below), which has only 9 carbons in the acyl chain of ceramide, produces predominately IL-4 and exhibits greater efficacy than KRN7000 against the autoimmune disease experimental allergic encephalomyelitis. (Pal, E et al., J Immunol., 166, 662 (2001); Miyamoto, K et al., Nature, 413, 531 (2001).) Whereas, the C-glycoside analogue of KRN7000, cKRN7000 (see structure below) upregulates IFN-.gamma. and is 100 times more potent than KRN7000 in inhibiting tumor growth in mice. (Yang, G et al., Angew. Chem. Int. Ed, 43, 3818 (2004).)"

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"One-Pot Synthesis of Alpha/Beta-O-Clycolipids"... [Published 4 Traders - Aug 21 2014]
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