アブストラクト(49巻2号:神奈川歯学)

神奈川歯学

Japanese

Title : Porphyromonas gingivalis lipid Aの合成戦略 - 光学活性β-ヒドロキシ脂肪酸の新規光学分割法 -
Subtitle : 原著
Authors : 熊田秀文, 佐藤武則*, 遠藤生**, 藤岡隼**, 築山光一**, 浜田信城*, 藤本賢二***
Authors(kana) :
Organization : 神奈川歯科大学大学院歯学研究科歯学教育学講座, *神奈川歯科大学大学院歯学研究科微生物感染学講座, **東京理科大学大学院総合化学研究科, ***(株)藤本分子化学
Journal : 神奈川歯学
Volume : 49
Number : 2
Page : 134-140
Year/Month : 2014 / 12
Article : 原著
Publisher : 神奈川歯科大学学会
Abstract : 「緒言」Porphyromonas gingivalisは, 歯周疾患に深く関連する細菌であることが多くの研究により示唆されている. 近年, P.gingivalis (Pg) は, 慢性歯周炎の活動部位あるいは重度の歯周炎病巣から, Tannerella forsythensisおよびTreponema denticolaと共に分離され, これら3菌種の共存はRed Complexとして歯周疾患の臨床において重要視されている. しかしながら, Pgの病原因子の一つであるリポ多糖 (lipopolysaccharide, LPS) は, ヒト歯肉線維芽細胞における炎症性サイトカイン産生促進や骨吸収活性を示すにも関わらず, 多くの生物活性がEscherichia coli LPSと比較して約1/10~1/100弱いこと, また, マイトジェン活性やLPS非応答性C3H/HeJマウス細胞に対して活性を示すことなどの結果から, 近年までユニークな活性を持つLPSとして議論されている.
Practice : 歯科学
Keywords : Porphyromonas gingivalis, Lipopolysaccharide (LPS), β-ヒドロキシ脂肪酸, 化学合成

English

Title : Strategy for the chemical synthesis of Porphyromonas gingivalis lipid A - New optical resolution for a racemic mixture of β-hydroxy fatty acids -
Subtitle :
Authors : Hidefumi KUMADA, Takenori SATO*, Ikuru ENDO**, Jun FUJIOKA**, Koichi TSUKIYAMA**, Nobushiro HAMADA*, Kenji FUJIMOTO***
Authors(kana) :
Organization : Department of Dental Education, Graduate School of Dentistry, Kanagawa Dental University, *Department of Microbiology, Graduate School of Dentistry, Kanagawa Dental University, **Graduate School of Chemical Science and Technology, Tokyo University of Science, ***Fuji Molecular Planning Co.,Ltd.
Journal : Kanagawa Shigaku
Volume : 49
Number : 2
Page : 134-140
Year/Month : 2014 / 12
Article : Original article
Publisher : Kanagawa Odontological Society
Abstract : [Abstract] Lipid A from the periodontal pathogen Porphyromonas gingivalis is an immunologically active substance. Purified samples of lipid A, with a minimal amount of protein, from cultured bacterial cells contains a heterogeneous mixture of molecules due to differing amounts of phosphates and fatty acids attached to the glucosamine backbone. In order to identify the species of molecules that elicit the most potent endotoxic effects and immunological activities it is essential to chemically synthesize enantiomerically pure lipid A. However, previous synthetic approaches have been frustrated by the non-availability of commercial iso-fatty acids and the very low enatiomeric purity of β-hydroxy fatty acids. In addition, chemical synthesis of complete lipid A molecules requires multiple steps, making the process both time consuming and costly as well as resulting in a low purity product in low chemical yield. Therefore, the development of simple and robust techniques for the synthesis of enantiomerically pure lipid A in good chemical yield will be of enormous benefit. Here, we describe a method involving the insertion of β-lactone into chiral β-hydroxy fatty acids (C15-C17) as a protecting group. The resulting protected β-hydroxy fatty acids were then resolved using a lipase. The final product contained predominantly (R)-β-hydroxy fatty acids : (R)-iso-C15-β-lactone, (R)-C16-β-lactone and (R)-iso-C17-β-lactone. Hence, this novel technique enabled us to obtain high enantioselectivity in good chemical yield. We believe our strategy will contribute to the development of simplified methods for the synthesis of enantiomerically pure lipid A of P. gingivalis. Therefore, this approach may help identify the species of lipid A molecules that have pathogenic and immunological activities.
Practice : Dentistry
Keywords : Porphyromonas gingivalis, Lipopolysaccharide (LPS)