Structural Study on Small Molecules in Biological Solid Samples by Using Solid State NMR

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Other Title
  • 固体NMRを利用した生物固体試料内小分子化合物の構造研究
  • コタイ NMR オ リヨウ シタ セイブツ コタイ シリョウ ナイ ショウブンシ カゴウブツ ノ コウゾウ ケンキュウ

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Description

  Many small molecule drugs have molecular targets that are non-crystalline and insoluble biological matrices, such as proteins embedded in lipid membrane, cell membranes, and cell walls. To understand the action mechanisms, it is essential to determine the binding structure with atomic-level resolution. Although solution nuclear magnetic resonance (NMR) and X-ray crystallography have been used to determine molecular structures of cell membrane and membrane proteins, these methods are unable to reproduce the complexity of biological systems because either solubilization or crystallization of target molecules is requisite. For structural studies of insoluble non-crystalline biological samples, so-called “biological solids”, high resolution distance measurements using solid-state NMR are indispensable techniques, of which rotational-echo double-resonance (REDOR) is one of the most widely used methods. In this paper, a brief introduction to REDOR NMR and its applications to structural studies on the antifungal amphotericin B-membrane phospholipid complex and a structural elucidation of photorespiration metabolites in plant cells without extraction or isolation is provided.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 132 (9), 969-978, 2012-09-01

    The Pharmaceutical Society of Japan

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