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α-Galactosyl Phytosphingosine 2,6’-Diamide as an Inducer of Invariant Natural Killer T Cell

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DOI: 10.4236/ojmc.2013.33008    2,818 Downloads   4,850 Views  


Four a-galactosyl phytosphingosine 2,6’-diamide analogs were prepared from 2,6’-diamino a-galactosylphytosphingosine and the aromatic-bearing carboxylic acids. After purification with High Performance Liquid Chromatography, a flowcytometry for the four compounds for stimulation of human Va24+/Vb11+ NKT cell populations was carried out. Additional keto groups on the acyl chains of the 2,6’-diamide compound was associated with the enhanced stimulating effect.

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Y. Huang, W. Chen, S. Tien, H. Huang, C. Yeh, K. Lin and C. Yu, "α-Galactosyl Phytosphingosine 2,6’-Diamide as an Inducer of Invariant Natural Killer T Cell," Open Journal of Medicinal Chemistry, Vol. 3 No. 3, 2013, pp. 55-59. doi: 10.4236/ojmc.2013.33008.


[1] T. Natori, M. Morita, K. Akimoto and Y. Koezuka, “Age- lasphins, Novel Antitumor and Immunostimulatory Cerebrosides from the Marine Sponge Agelas-Mauritianus,” Tetrahedron, Vol. 50, No. 9, 1994, pp. 2771-2784. doi:10.1016/S0040-4020(01)86991-X
[2] M. Morita, K. Motoki, K. Akimoto, T. Natori, T. Sakai, E. Sawa, K. Yamaji, Y. Koezuka, E. Kobayashi and H. Fukushima, “Structure-Activity Relationship of Alpha-Galactosylceramides Against B16-Bearing Mice,” Journal of Medicinal Chemistry, Vol. 38, No. 12, 1995, pp. 2176- 2187. doi:10.1021/jm00012a018
[3] M. Skold and S. M. Behar, “Role of CD1d-Restricted NKT Cells in Microbial Immunity,” Infection and Immunity, Vol. 71, No. 10, 2003, pp. 5447-5455. doi:10.1128/IAI.71.10.5447-5455.2003
[4] A. Bendelac, P. B. Savage and L. Teyton, “The Biology of NKT Cells,” Annual Review of Immunology, Vol. 25, 2007, pp. 297-336. doi:10.1146/annurev.immunol.25.022106.141711
[5] M. J. Smyth, N. Y. Crowe, Y. Hayakawa, K. Takeda, H. Yagita and D. Godfrey, “NKT Cells-Conductors of Tumor Immunity?” Current Opinion in Immunology, Vol. 14, No. 2, 2002, pp. 165-171. doi:10.1016/S0952-7915(02)00316-3
[6] K. J. L. Hammond and D. I. Godfrey, “NKT Cells: Potential Targets for Autoimmune Disease Therapy?” Tissue Antigens, Vol. 59, No. 5, 2002, pp. 353-363. doi:10.1034/j.1399-0039.2002.590501.x
[7] C. R. Berkers and H. Ovaa, “Immunotherapeutic Potential for Ceramide-Based Activators of iNKT Cells,” Trends in Pharmacological Sciences, Vol. 26, No. 5, 2005, pp. 252- 257. doi:10.1016/
[8] J. Wojno, J. P. Jukes, H. Ghadbame, D. Shepherd, G. S. Bersa, V. Gerundolo and L. R. Cox, “Amide Analogs of CD1d Agonists Modulate iNKT-Cell-Mediated Cytokine Production,” ACS Chemical Biology, Vol. 7, No. 5, 2012, pp. 847-855. doi:10.1021/cb2005017
[9] J. Hunault, M. Diswall, J. C. Trison, V. Blet, J. Pocher, S. Marionneau-Lambt, T. Oullier, J.-Y. Douillard, S. Guillarme, C. Saluzzo, G. Dujardin, D. Jacqomin, J. Graton, J.-Y. Le Ouestel, M. Evain, J. Lebreton, D. Dubreuil, J. Le Pendu and M. Pipelier, “3-Fluoroand 3,3-Difluoro- 3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice,” Journal of Medicinal Chemistry, Vol. 55, No. 3, 2012, pp. 1227-1241. doi:10.1021/jm201368m
[10] N. Veerapen, E. A. Leadbetter, M. B. Brenner, L. R. Cox and G. S. Bersa, “Synthesis of a Novel-Galactosyl Ceramidic Hepatenated-Lipid Antigen, a Useful Tool in Demonstrating the Involvement of iNKT Cells in the Production of Antilipid Antibodies,” Bioconjugate Chemistry, Vol. 21, No. 4, 2010, pp. 741-747. doi:10.1021/bc9005255
[11] P. I. Kitov, J. M. Sadowska, G. Mulvey, G. D. Armstrong, H. Ling, N. S. Pannu, R. J. Read and D. R. Bundle, “Shiga-Like Toxins Are Neutralized by Tailored Multivalent Carbohydrate Ligands,” Nature, Vol. 403, No. 6770, 2000, pp. 669-672. doi:10.1038/35001095
[12] R. W. Franck and M. Tsuji, “?-C-Galactosyl Ceramides: Synthesis and Immunology,” Accounts of Chemical Research, Vol. 39, No. 10, 2006, pp. 692-701. doi:10.1021/ar050006z
[13] Y.-C. Huang, L.-W. Chiang, K.-S. Chang, W.-C. Su, Y.- H. Lin, K.-C. Jeng, K.-I. Lin, K.-Y. Liao, H.-L. Huang and C.-S. Yu, “Synthesis of Amino Core Compounds of Galactosyl Phytosyl Ceramide Analogs for Developing iNKT-Cell Inducers,” Molecules, Vol. 17, No. 3, 2012, pp. 3058-3081. doi:10.3390/molecules17033058
[14] M. Michieletti, A. Bracci, F. Compostella, G. De Libero, L. Mori, S. Fallarini, G. Lombard and L. Panza, “Synthesis of α-Galactosyl Ceramide (KRN7000) and Analogs Thereof via a Common Precursor and Their Preliminary Biological Assessment,” The Journal of Organic Chemistry, Vol. 73, No. 22, 2008, pp. 9192-9195. doi:10.1021/jo8019994
[15] J. Lopez-Sagaseta, J. E. Kung, P. B. Savage, J. Gumperz and E. J. Adams, “The Molecular Basis for Recognition of CD1d/Alpha-Galactosylceramide by a Human Non-V alpha 24 T Cell Receptor,” PLOS Biology, Vol. 10, No. 10, 2012, p. e1001412. doi:10.1371/journal.pbio.1001412
[16] D. G. Pellicci1, A. J. Clarke, O. Patel, T. Mallevaey, T. Beddoe, J. Le Nours, A. P. Uldrich, J. McCluskey, G. S. Besra, S. A. Porcelli, L. Gapin, D. I. Godfrey and J. Rossjohn, “Recognition of β-Linked Self Glycolipids Mediated by Natural Killer T Cell Antigen Receptors,” Nature Immunology, Vol. 12, No. 9, 2011, pp. 827-834. doi:10.1038/ni.2076

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