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Dimers formed with the mixed-type G-quadruplex binder pyridostatin specifically recognize human telomere G-quadruplex dimers.
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2020-01-10 , DOI: 10.1039/c9ob02470k
Tian-Zhu Ma 1 , Meng-Jia Zhang 1 , Ting-Cong Liao 1 , Jun-Hui Li 1 , Min Zou 1 , Zhou-Mo Wang 2 , Chun-Qiong Zhou 1
Affiliation  

By choosing pyridostatin (PDS) with high thermal stabilization towards mixed-type G-quadruplexes as the monomer in dimers, three novel polyether-tethered PDS dimers (1a-c) were first synthesized and their interaction with human telomere G-quadruplex dimers (G2T1) was studied. Through the regulation of the linker length in PDS dimers, the dimer with a medium-length polyether linker (1b) showed higher binding selectivity and thermal stabilization (ΔTm = 29.5 °C) towards antiparallel G2T1 over G-quadruplex monomers (G1). Furthermore, the dimer with the longest-length polyether linker (1c) showed higher binding selectivity and thermal stabilization towards mixed-type G2T1 over mixed-type G1, c-kit 1, c-kit 2, c-myc and ds DNA. This work provides new insights into the development of G2T1 binders, especially mixed-type G2T1 binders, which could be promoted by a polymer formed with a mixed-type G-quadruplex binder. In addition, dimer 1c exhibited stronger telomerase inhibition than dimers 1a and 1b.

中文翻译:

与混合型G-四链体吡啶斯达汀形成的二聚体可特异性识别人端粒G-四链体二聚体。

通过选择对混合型G-四链体具有高热稳定性的吡ido他汀(PDS)作为二聚体中的单体,首先合成了三个新型的聚醚系PDS二聚体(1a-c),它们与人端粒G-四链体二聚体(G2T1)相互作用)进行了研究。通过调节PDS二聚体中的连接体长度,具有中等长度聚醚连接体(1b)的二聚体对G-四链体单体(G1)的反平行G2T1表现出更高的结合选择性和热稳定性(ΔTm= 29.5°C)。此外,与混合型G1,c-kit 1,c-kit 2,c-myc和ds DNA相比,具有最长长度的聚醚接头(1c)的二聚体对混合型G2T1表现出更高的结合选择性和热稳定性。这项工作为G2T1粘合剂(尤其是混合型G2T1粘合剂)的开发提供了新见解,它可以由与混合型G-四链体粘合剂形成的聚合物促进。另外,二聚体1c比二聚体1a和1b表现出更强的端粒酶抑制作用。
更新日期:2020-02-13
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