RESUMO
Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene, 2), an oxygenated analog of resveratrol (1), was synthesized. It is one of the naturally occurring polyphenolic stilbenoids contained in red wine, and possesses many kinds of beneficial effects such as anticancer activity. The trans-stilbene skeleton of 2 was constructed by Pd-catalyzed Suzuki-Miyaura cross coupling reaction of triflate 8 with (E)-alkenylboronoate 13. The key intermediate 13 was prepared diastereoselectively by acid-catalyzed hydroboration of pinacolborane 12 to alkyne 11.
Assuntos
Resveratrol/análogos & derivados , Estilbenos/síntese química , Estrutura MolecularRESUMO
Establishment of a system with efficient generation of natural killer T (NKT) cells from embryonic stem (ES) cells would enable us to identify the cells with NKT-cell potential and obtain NKT cells with desired function. Here, using cloned ES (NKT-ES) cells generated by the transfer of nuclei from mature NKT cells, we have established a culture system that preferentially developed functional NKT cells and also identified early NKT progenitors, which first appeared on day 11 as a c-kit(+) population in the cocultures on OP9 cells with expression of Notch ligand, delta-like1 (OP9/Dll-1) and became c-kit(lo/-) on day 14. Interestingly, in the presence of Notch signals, NKT-ES cells differentiated only to thymic CD44(lo) CD24(hi) NKT cells producing mainly interleukin-4 (IL-4), whereas NKT cells resembling CD44(hi) CD24(lo) liver NKT cells producing mainly interferon gamma (IFN-gamma) and exhibiting strong adjuvant activity in vivo were developed in the switch culture starting at day 14 in the absence of Notch. The cloned ES culture system offers a new opportunity for the elucidation of the molecular events on NKT-cell development and for the establishment of NKT-cell therapy.
Assuntos
Diferenciação Celular/imunologia , Núcleo Celular/imunologia , Células-Tronco Embrionárias/imunologia , Células T Matadoras Naturais/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Animais , Antígeno CD24/imunologia , Antígeno CD24/metabolismo , Proteínas de Ligação ao Cálcio , Núcleo Celular/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Receptores de Hialuronatos/imunologia , Receptores de Hialuronatos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Células T Matadoras Naturais/citologia , Células T Matadoras Naturais/metabolismo , Técnicas de Transferência Nuclear , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores Notch/imunologia , Receptores Notch/metabolismo , Fatores de TempoRESUMO
Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-gamma, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.