P-51 昆虫機能を利用した自然免疫制御物質の探索と創薬への展開(ポスター発表の部)

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Innate immunity is the first line of defense against infectious microorganisms. The basic mechanisms of pathogen recognition and response activation are evolutionarily conserved. In mammals, the innate immunity has an instructive role in the adaptive immune response specific to antigen by inducing co-stimulatory molecules and cytokines, indicating that a concerted and interactive innate and adaptive immune reaction is key for the regulated immune response. Therefore, from a pharmaceutical point of view, innate immunity is a good target for the development of immune regulators to suppress unwanted immune responses, such as septic shock, inflammatory diseases and autoimmunity, and to stimulate protective immune responses to some of the disease that largely elude the immune system, such as infectious diseases and cancer. For pharmaceutical screening, we established an in vitro culture based on the innate immune response of Drosophila, which is equivalent to that of mammals. The expression of a reporter gene, Dpt-lac Z, reflected the LPS-dependent activation of innate immunity. Search for natural substances regulating innate immunity by the systems led us the isolation of 17 compounds including a cyclopentanediol derivative, TP-1 (1), and a ceramide derivative, TP-76 (2), as innate immune suppressors. Furthermore, we synthesized some derivatives of TP-1 to evaluate structure-activity relationship of these compounds. Methylamide, phenylamide and methylsulfoneamide analogs exhibited innate immune suppressive activities 15 times more potent than that of TP-1 (1).
天然有機化合物討論会の論文
2007-08-24

P-51 昆虫機能を利用した自然免疫制御物質の探索と創薬への展開(ポスター発表の部)

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