放線菌の代謝産物を求めて―抗ウイルス薬と酵素阻害薬―

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  • 上田 勝
    熊本大学大学院医学薬学研究部薬学微生物学分野

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タイトル別名
  • Metabolites Produced by Actinomycetes-Antiviral Antibiotics and Enzyme Inhibitors-
  • ホウセンキン ノ タイシャ サンブツ オ モトメテ コウウイルスヤク ト コウソ ソガイヤク

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説明

  In 1995, we discovered new antiherpetic antibiotics, called fattiviracins. The producing organism was classified as a strain belonging to Streptomyces microflavus. The strain produced at least 13 fattiviracin derivatives (FV-1 to FV-13). Fattiviracins were obtained as a white amorphous powder, and their molecular weights are in the range of 1400 to 1500. They are readily soluble in water, methanol, pyridine, and DMSO, but insoluble in other organic solvents. Fattiviracins have macrocyclic diesters formed by the binding of two trihydroxy fatty acids and two D-glucose residues in the molecule, and they can be divided into five families according to the length of the fatty acid moiety. Fattiviracins have potent activity against enveloped DNA viruses such as the herpes family, HSV-1, and VZV and enveloped RNA viruses such as influenza A and B viruses, and three strains of HIV-1, with EC50 values on the order of a few micrograms per milliliter. The biosynthetic pathway of fattiviracins is also becoming clearer. Using bacitracin-resistant strains, enhanced and astringent production of fattiviracin was achieved. Fattiviracin FV-13, which has the longest fatty acid chains in the molecule, was dramatically enhanced by a C55-isoprenyl phosphate metabolism. In addition, we have screened various inhibitors of enzymes such as alkaline protease, glucosyltransferase, glucuronidase, phospholipase, deoxyribonuclease, DNA methyltransferase, and DNA topoisomerase. All the inhibitors we discovered are briefly summarized in this paper.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 124 (8), 469-479, 2004

    公益社団法人 日本薬学会

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