Spatial Matching Selectivity and Solution Structure of Organic-Metal Hybrid to Quadruplex-Duplex Hybrid
Spatial Matching Selectivity and Solution Structure of Organic-Metal Hybrid to Quadruplex-Duplex Hybrid
复制标题
有机金属杂化物与四链体-双链体杂化物的空间匹配选择性和溶液结构
DOI：
10.1002/anie.202106256
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发表时间：
2021-08-17
影响因子：
16.6
通讯作者：
Mao, Zong-Wan
中科院分区：
文献类型：
--
作者：
Liu, Liu-Yi;Wang, Kang-Nan;Mao, Zong-Wan
序列依赖性DNA二级结构具有结构多态性。迄今为止，对调节配体的研究主要关注单个DNA二次拓扑，而缺乏重点是四链链链夹混合体（QDHS）。在这里，我们设计了一种有机金属杂种配体（LPT）-PT-1（DIEN），该配体与具有高亲和力的侧向双层茎环（QLDH）匹配并有选择地结合一种QDH，而对其他QDH的亲和力较差和单个G4或双链DNA。 NMR确定了QLDH myt1l-（LPT）-PT-1（DIEN）复合物的溶液结构。该结构表明（LPT）-PT-1（DIEN）提出了一个椅子构象，其大的芳香族“椅子表面”通过PI-PI堆叠和“ Backrest” Platinum单位与G-Quadruplex-Duplex界面插入到G- Quadruplex-duplex界面中通过氢键和静电相互作用的双链区域，显示了高度匹配的锁紧结合模式。我们的工作为有选择地靶向QDH结构的靶向配体的空间匹配设计提供了指导。
The sequence-dependent DNA secondary structures possess structure polymorphism. To date, studies on regulated ligands mainly focus on individual DNA secondary topologies, while lack focus on quadruplex-duplex hybrids (QDHs). Here, we design an organic-metal hybrid ligand (LPt)-Pt-1(dien), which matches and selectively binds one type of QDHs with lateral duplex stem-loop (QLDH) with high affinity, while shows poor affinity for other QDHs and individual G4 or duplex DNA. The solution structure of QLDH MYT1L-(LPt)-Pt-1(dien) complex was determined by NMR. The structure reveals that (LPt)-Pt-1(dien) presents a chair-type conformation, whose large aromatic "chair surface" intercalates into the G-quadruplex-duplex interface via pi-pi stacking and "backrest" platinum unit interacts with duplex region through hydrogen bonding and electrostatic interactions, showing a highly matched lock-key binding mode. Our work provided guidance for spatial matching design of selectively targeting ligands to QDH structures.