Ueki T, Numata K, Sawada Y, Nishio M, Ohkuma H, Toda S, Kamachi H, Fukagawa Y, Oki T
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
J Antibiot (Tokyo). 1993 Mar;46(3):455-64. doi: 10.7164/antibiotics.46.455.
Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D-mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium. The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation. The stereospecific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety. Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test.
基于BMY-28864及相关普拉迪米星衍生物的构效关系数据，在BMY-28864与D-甘露吡喃糖苷和钙形成三元复合物的过程中，分析了BMY-28864的钙盐形成能力以及D-甘露吡喃糖苷特异性可见吸收最大值的变化。结果表明，BMY-28864的游离C-18羧基是与钙结合的唯一部位，而苷元的羟基不参与钙盐的形成。去除C-5二糖部分，尤其是C-5硫代氨基糖部分后，BMY-28864的立体特异性D-甘露吡喃糖苷识别能力完全丧失。体外抗真菌试验和钾泄漏诱导试验也支持了这些发现与抗真菌作用的密切关系。
