Bergan R, Connell Y, Fahmy B, Kyle E, Neckers L
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Nucleic Acids Res. 1994 Jun 11;22(11):2150-4. doi: 10.1093/nar/22.11.2150.
Protein tyrosine kinases play key roles in cellular physiology. Specific inhibitors of these enzymes are important laboratory tools and may prove to be novel therapeutic agents. In this report we describe a new class of tyrosine kinase inhibitor, synthetic oligodeoxynucleotides (ODNs). An ODN is described which specifically inhibits p210bcr-abl tyrosine kinase autophosphorylation in vitro with a Ki of 0.5 microM. Inhibition is non-competitive with respect to ATP. The effects upon inhibitory activity of ODN structure modifications are described. The inhibition described is not mediated by classical antisense mechanisms and represents an example of the recently recognized aptameric properties of ODNs.
蛋白质酪氨酸激酶在细胞生理学中发挥关键作用。这些酶的特异性抑制剂是重要的实验室工具，并且可能被证明是新型治疗药物。在本报告中，我们描述了一类新型酪氨酸激酶抑制剂，即合成寡脱氧核苷酸（ODN）。描述了一种ODN，它在体外能特异性抑制p210bcr-abl酪氨酸激酶的自身磷酸化，其抑制常数（Ki）为0.5微摩尔。这种抑制作用对ATP而言是非竞争性的。描述了ODN结构修饰对其抑制活性的影响。所描述的抑制作用不是由经典的反义机制介导的，而是最近所认识到的ODN适配体特性的一个例子。
