Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent
Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent
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DOI：
10.1016/j.bmc.2018.05.030
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发表时间：
2018-07-23
影响因子：
3.5
通讯作者：
Nagatsugi, Fumi
中科院分区：
文献类型：
--
作者：
Hazemi, Madoka E.;Onizuka, Kazumitsu;Nagatsugi, Fumi
核酸的高阶结构因其生物学意义而受到广泛关注，而这些结构的烷基化小分子的发现由于其治疗潜力而引起人们的兴趣。我们之前开发了乙烯基二氨基三嗪(VDAT)-吖啶缀合物作为T-T错配烷基化剂。在这篇报道中，我们重点发现了vdat -吖啶缀合物与g -四重体（G4） DNA的烷基化。在温和的条件下，vdat -吖啶偶联物对G4表现出相当大的烷基化能力。此外，对烷基化G4的性能研究表明，该共轭物的烷基化显著提高了G4结构的稳定性。本研究为进一步开发选择性烷基化小分子G4提供了一个起点。
Higher-order structures of nucleic acids have become widely noted for their biological consequences and the discovery of an alkylating small molecule for these structures has been of interest due to its therapeutic potential. We previously developed the vinyldiaminotriazine (VDAT)-acridine conjugate as a T-T mismatch alkylating agent. In this report, we focused on the finding of the alkylation to the G-quadruplex (G4) DNA with VDAT-acridine conjugates. The VDAT-acridine conjugates exhibited a considerable alkylation ability to G4 under mild conditions. Moreover, the investigation of properties with the alkylated G4 revealed that alkylation by this conjugate significantly increased the stability of the G4 structure. This study provides a starting point in the further development of selective G4 alkylating small molecules.