83(P75) 放線菌の気菌糸誘導物質pamamycinsの構造活性相関と作用機構(ポスター発表の部)

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Pamamycins, a novel family of macrodiolides with MW's ranging from 593 to 663, are produced by Streptomyces alboniger IFO 12738. Pamamycin-607 (MW 607) has aerial mycelium-inducing activity in an aerial mycelium-less mutant of S. alboniger. We examined the structure-activity relationship of pamamycins in view of alkyl substit-uents, dimethylamino group and macrodiolide ring. Nine new pamamycin homologues with MWs 593, 621 and 635 were isolated using a combination of ODS and NH_2 HPLCs, and their structures determined by GC-MS. The aerial mycelium-inducing activity mostly was lost when R_3 or R_4 was changed from CH_3 to C_2H_5. Replacement of the other alkyl substituents, R_1, R_2 and R_5, caused a drop to 30-40% of the original activities. In consideration with CPK model, pamamycin-607 has the conformation that both R_3 and R_4 extend from one side of the molecule. Next, we prepared a desdimethylamino derivative, a ring-opened compound and two constituent hydroxy acids by chemically degrading pamamycin-607, and examined their aerial mycelium-inducing activity. Desdimethylamino derivative lost activity, indi-cating that dimethylamino group was indispensable for activity. The ring-opened com-pound showed about 1/2 the activity of pamamycin-607, whereas the larger hydroxy acid had only 1/30 of the activity and the smaller acid had no activity. Thus, the larger hydroxy acid part was the principal component responsible for activity and the smaller hydroxy acid part may help the activity of the larger hydroxy acid part. We found that Ca^<2+> regulates the aerial mycelium formation of many actinomycetes including S. alboniger and that Ca^<2+> signal modulators such as Ca^<2+> channel blockers and calmodulin inhibitors inhibit aerial mycelium formation of S. alboniger. Based on these observations, we examined the effects of pamamycin-607 on intracellular concen-tration of Ca^<2+>. As a result, pamamycin-607 induced a transient increase in the intracellular concentration of Ca^<2+> dose-dependently.
天然有機化合物討論会の論文
1996-09-02

83(P75) 放線菌の気菌糸誘導物質pamamycinsの構造活性相関と作用機構(ポスター発表の部)

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