Institute of Chemistry, University of Tartu, 14A Ravila St., 50411 Tartu, Estonia.
Institute of Chemistry, University of Tartu, 14A Ravila St., 50411 Tartu, Estonia.
Bioorg Med Chem. 2018 Oct 1;26(18):5062-5068. doi: 10.1016/j.bmc.2018.09.003. Epub 2018 Sep 5.
A previously disclosed protein kinase (PK) CK2-selective inhibitor 4-(2-amino-1,3-thiazol-5-yl)benzoic acid (ATB) and its selenium-containing counterpart (ASB) revealed remarkable room temperature phosphorescence when bound to the ATP pocket of the protein kinase CK2. Conjugation of these fragments with a mimic of CK2 substrate peptide resulted in bisubstrate inhibitors with increased affinity towards the kinase. Attachment of the fluorescent acceptor dye 5-TAMRA to the conjugates led to significant enhancement of intensity of long-lifetime (microsecond-scale) photoluminescence of both sulfur- and selenium-containing compounds. The developed photoluminescent probes make possible selective determination of the concentration of CK2 in cell lysates and characterization of CK2 inhibitors by means of time-gated measurement of photoluminescence.
先前披露的蛋白激酶（PK）CK2 选择性抑制剂 4-（2-氨基-1,3-噻唑-5-基）苯甲酸（ATB）及其含硒类似物（ASB）在与蛋白激酶 CK2 的 ATP 口袋结合时，显示出显著的室温磷光。将这些片段与 CK2 底物肽的模拟物连接，得到了双底物抑制剂，它们对激酶的亲和力增加。将荧光受体染料 5-TAMRA 连接到缀合物上，导致含硫和硒化合物的长寿命（微秒级）光致发光强度显著增强。开发的光致发光探针使得有可能通过时间门控测量光致发光来选择性地确定细胞裂解物中 CK2 的浓度，并通过时间门控测量光致发光来表征 CK2 抑制剂。
