Identification of novel peptidomimetics targeting the polo-box domain of polo-like kinase 1
Identification of novel peptidomimetics targeting the polo-box domain of polo-like kinase 1
复制标题
鉴定针对 polo 样激酶 1 的 polo-box 结构域的新型肽模拟物
DOI：
10.1016/j.bioorg.2019.103148
复制
发表时间：
2019
影响因子：
5.1
通讯作者：
Jiang Cheng
中科院分区：
文献类型：
--
作者：
Li Zhiyan;Zhang Zhenguo;Sun Huiyong;Xu Lili;Jiang Cheng
A series of new peptidomimetics targeting the polo-box domain (PBD) of polo-like kinase 1 (Plk1) was identified based on the potent and selective pentapeptide Plk1 PBD inhibitor PLHSpT. Unnatural amino acid residues were introduced to the newly designed compound and theN-terminal substituent of the peptidomimetic was investigated. The optimized compound9inhibited the Plk1 PBD with IC50of 0.267 μM and showed almost no inhibition to Plk2 PBD or Plk3 PBD at 100 μM. Biolayer interferometry studies demonstrated that compound9showed potent binding affinity to Plk1 with aKdvalue of 0.164 μM, while noKdwere detected against Plk2 and Plk3. Compound9showed improved stability in rat plasma compared to PLHSpT. Binding mode analysis was performed and in agreement with the observed experimental results. There are only two natural amino acids remained in the chemical structure of9. This study may provide new information for further research on Plk1 PBD inhibitors.
