ENZYME INHIBITORS AS PROTENTIAL ANTICANCER AND ANTIVIRAL DRUGS

我们生产PK-C-交互试剂的合成战略已经开始 二酰甘油类似物嵌入更复杂的环中 限制药理作用基团取向的结构。这 该方法已经产生了稳定的合成化合物，其亲和力(KI)为 10纳米，已经在佛波醇酯的范围内。向下的模式 我们最有效的基因对蛋白激酶C同工酶的调节作用 化合物不同于典型的促癌佛波酯， TPA。这改变了监管的下调，这是两家公司的标志 已知的一类调节结构域靶向的蛋白激酶C抑制剂， Bryostatins和Prostratin，表明同样的效果可以 通过更简单和更容易合成的分子来实现。

Our synthetic strategy to produce PK-C-interactive agents has started with diacylglycerol analogues embedded in more complicated ring structures to constrain orientation of pharmacophoric groups. This approach has yielded stable synthetic compounds with affinities (Ki) of 10 nM, already in the range of phorbol esters. The pattern of down regulation of protein kinase C isozymes induced by the most potent of our compounds differs from that of the typical tumor promoting phorbol ester, TPA. This altered down regulation which is the hallmark for the two known classes of regulatory domain-targeted protein kinase C inhibitors, the bryostatins and prostratin, indicates that the same effect can be achieved with simpler and more synthetically accessible molecules.