ピリミドインドール系TLR4リガンドの構造活性相関研究

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  • The study on structure-activity relationship of pyrimidoindoles TLR4 ligands
  • 【優秀演題賞】

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<p> Toll-like receptors (TLRs) are a family of type Ⅰ membrane proteins, classified to pattern recognition receptors (PRR). TLRs are expressed in cell surface or endosomal compartment of immune cells. TLRs are activated by recognition of pathogen specific components called pathogen-associated molecular patterns (PAMPs). Signal of TLRs induces the innate immune response and adaptive immune response. Therefore, TLRs play important roles in host defense system against viral or bacterial infection. In human, 10 kinds of TLR (TLR1 to TLR10) have been found. Each TLR recognizes different PAMP ; lipoprotein for TLR1/6 and TLR2/6 ; nucleic acid components for TLR3, -7, -8, and -9 ; lipopolysaccharide (LPS) for TLR4. TLRs are also activated by the specific endogenous danger signal (called damage-associated molecular pattern, DAMPs) produced by damaged tissue, which is thought to cause various chronic inflammatory diseases. On the other hand, low molecular weight TLR ligands have been found from natural and synthetic compounds, those can be candidates for development of chemical probes and drugs. In this review, focusing on TLR4, we describe recent progress in exploring TLR4 ligands with agonistic or antagonistic activity and our recent study on the structure-activity relationship of pyrimido [5,4-b] indole derivatives.</p>

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