SYNTHESIS AND CHARACTERIZATION OF FORSKOLIN DERIVATIVES

毛喉素衍生物的合成和表征

• 批准号: 3792429
• 负责人: J ROBBINS
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792429
• 关键词: adenylate cyclase; analog; chemical binding; chemical structure function; chemical synthesis; forskolin; glucose transport; glycoproteins; hydrogen bond

The diterpene forskolin has been demonstrated to affect proteins other than adenylyl cyclase. However, there has been relatively little information regarding the differences in the binding of forskolin at functionally diverse proteins. Analogs of forskolin have been developed which can be used to discriminate between adenylyl cyclase, the facilitated glucose transporter, and the P-glycoprotein multidrug transporter. The hydrogen binding requirements for forskolin interactions at the glucose transporter and the adenylyl cyclase have been determined and are very different. In addition, it has been shown that the affinity of forskolin for the Glut-4 glucose transporter is much higher than for the Glut-1 or Glut-3 transporter. However, the hydrogen bonding characteristics for forskolin binding to the Glut-1, Glut-3, and Glut-4 transporters are not very different. These data will be useful in developing a model for the forskolin binding site at the glucose transporter. Similar experiments are being carried out with adenylyl cyclase subtypes. In addition, experiments are being carried out to determine the structure activity relationships of forskolin for interactions with the P-glycoprotein multidrug transporter.

二萜类毛喉素已被证明影响蛋白质， 腺苷酸环化酶。 然而， 关于毛喉素结合的差异的信息， 功能多样的蛋白质。 毛喉素的类似物已经被开发出来 其可用于区分腺苷酸环化酶， 易化葡萄糖转运蛋白和P-糖蛋白多药 传送器。 毛喉素的氢键要求 葡萄糖转运蛋白和腺苷酸环化酶的相互作用 已经确定，并且非常不同。 此外，它已被证明 Forskolin对Glut-4葡萄糖转运蛋白的亲和力 比Glut-1或Glut-3转运蛋白高得多。 但 毛喉素与Glut-1结合的氢键特征， Glut-3和Glut-4转运蛋白没有很大的不同。 这些数据将 可用于开发毛喉素结合位点的模型 葡萄糖转运蛋白 类似的实验正在进行中， 腺苷酸环化酶亚型。 此外，正在进行实验， 旨在确定毛喉素的构效关系， 与P-糖蛋白多药转运蛋白的相互作用。