CHEMICAL STRUCTURE--HYPOTHALAMIC NA+/K+ ATPASE INHIBITOR

描述：下丘脑抑制因子，HIF，被认为是一种哺乳动物 洋地黄苷的类似物及其生物学和生化性质 与哺乳动物钠泵的生理调节一致 活体心血管、肾脏和神经系统组织。违反有关规定 抑制物-Na，K-ATPase系统与高血压的发病机制有关。 人类原发性高血压。纯HIF的结构分析表明 是植物糖苷的类固醇部分不同的异构体， 哇巴因。近年来，从人类体内分离得到一种哇巴因类化合物(OLC)。 血浆和感觉与植物哇巴因难以区分 重新研究发现，它与哇巴因不同，但与HIF相同， 进一步支持这样一个概念，即一种独特的分子可能特定地 调节人的Na，K-ATPase。最简单的解释与 我们的光谱数据是HIF与哇巴因的位置不同 鼠李糖苷异构体。我们合成了8个这样的过酰化类似物 得到了它们的CD光谱。无一例显示弱CD曲线(几乎为零)。 这是五萘甲酰HIF和OLC的签名，也没有计算CD 其余位置异构体的光谱，可能C5除外 鼠李糖苷。类固醇中可能存在更复杂的差异 在此基础上，建立了一种亲和纯化方法。 抗地高辛抗体，导致高产率纯HIF，使 内源性Na，K-ATPase抑制剂的完全结构归属 是可以实现的。鉴定HIF和HIF的单抗的研制 创建诊断化验是新提出的。

DESCRIPTION: Hypothalamic inhibitory factor, HIF, is felt to be a mammalian analog of the digitalis glycosides with biologic and biochemical properties consistent with physiologic regulation of the mammalian sodium pump in cardiovascular, renal and nervous system tissues in vivo. Disregulation of the inhibitor-Na,K-ATPase system has been linked to the pathogenesis of human essential hypertension. Structural analysis of pure HIF showed it to be an isomer, differing in the steroid moiety, of the plant glycoside, ouabain. Recently, an ouabain-like compound (OLC) isolated from human plasma and felt to be indistinguishable from plant ouabain has been restudied and found to be different from ouabain but identical to HIF, further supporting the notion that a unique molecule may specifically regulate the human Na,K-ATPase. The simplest explanation consistent with our spectroscopic data was that HIF differed from ouabain as a position isomer rhamnoside. We synthesized eight of these peracylated analogs and obtained their CD spectra. None of them showed weak CD curves (nearly zero) which is the signature of pentanaphthoyl HIF and OLC, nor did calculated CD spectra of remaining position isomers, with the possible exception of the C5 rhamnoside. With the likelihood of a more complex difference in the steroid moiety, an affinity purification method was developed using a monoclonal anti-digoxin antibody which resulted in high yields of pure HIF, making complete structural assignment of the endogenous Na,K-ATPase inhibitor achievable. Development of monoclonal antibodies to characterize HIF and create a diagnostic assay is newly proposed.