DESIGN OF NEW NUCLEOSIDES BASED ON ENZYME SPECIFICITIES

该项目的长期目标仍然是开发新的代理商 用于治疗人类癌症。因为大多数，如果不是全部的话， 目前用于治疗人类癌症的核苷必须 被磷酸化成它们的活性形式，我们计划更详细地研究 已知的进行这种激活的酶。脱氧胞苷 激酶是启动这一过程的主要酶，但不是唯一的。 激活过程，所以我们计划与Dr合作专注于它。 密歇根大学的唐娜·S·谢瓦赫。我们计划准备一个宽阔的 一系列化合物，重点是它们激活酶以及 它们的抗肿瘤选择性。 我们还计划检查我们收集的核苷三磷酸盐 端粒酶抑制物，一种在人类体内被激活的DNA聚合酶 癌症。研究将显示我们手头有或很容易就有三磷酸盐 生成并将向我们提供将用于 设计新的化合物，这些化合物将是对此更特异的抑制剂 酶，这似乎是CAN化疗的一个重要的新靶点。

The long-term goal of this project remains the development of new agents for the treatment of human cancers. Since most, if not all, of the nucleosides currently in use for the treatment of human cancers must phosphorylated to their active forms, we plan to investigate in some detail the enzymes that are known to carry out this activation. Deoxycytidine kinase is the primary, but not the only, enzyme that initiates this activation process, so we plan to focus on it, in collaboration with Dr. Donna S. Shewach of the University of michigan. We plan to prepare a broad series of compounds with a focus on them activating enzymes as well as their antitumor selectivity. We also plan to examine our collection of nucleoside triphosphates as inhibitors of telomerase, a DNA polymerase which is activated in human cancers. The studies will show triphosphates we have on hand or easily generate, and will provide us with SAR information that will be used in designing new compounds that will be more specific inhibitors for this enzyme, which appears to be an important new target for can chemotherapy.