当前位置: X-MOL 学术Nucleic Acids Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes.
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2020-01-08 , DOI: 10.1093/nar/gkz1205
Rajendra Kumar 1 , Karam Chand 1 , Sudipta Bhowmik 1, 2 , Rabindra Nath Das 1 , Snehasish Bhattacharjee 2 , Mattias Hedenström 1 , Erik Chorell 1
Affiliation  

G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.

中文翻译:

G-四链体DNA中的细微结构改变调节了荧光发光探针的位点特异性。

G-四链体(G4)DNA结构与关键的生物过程和人类疾病有关。因此,靶向特定G4 DNA结构并发出信号指示其存在的小分子作为化学研究工具具有巨大的价值,并且有可能进一步推进诊断和治疗的发展。但是,开发这些类型的特定化合物仍然是一个巨大的挑战。在这里,我们开发了一种具有通过荧光发光机制特异性发出某些c-MYC G4 DNA结构信号的能力的化合物。尽管该化合物在G4 DNA结构上有两个结合位点,但只有一个会导致荧光发光。事实证明,这种G-tetrad选择性来自于柔韧性差异,柔韧性差异会影响结合亲和力,并使化合物脱离荧光发光机理所需的平面构象。提出的因素之间的相互联系可能是缺乏使用合理设计来开发具有特定靶标某些G4 DNA结构的开启发射特性的化合物的例子的原因。但是,这项研究表明,确实有可能开发出此类化合物,并提供有关特定G4 DNA识别和信号传导分子细节的见识,以推动G4生物学的进一步研究。提出的因素之间的相互联系可能是缺乏使用合理设计来开发具有特定靶标某些G4 DNA结构的开启发射特性的化合物的例子的原因。但是,这项研究表明,确实有可能开发出此类化合物,并提供有关特定G4 DNA识别和信号传导分子细节的见识,以推动G4生物学的进一步研究。提出的因素之间的相互联系可能是缺乏使用合理设计来开发具有特定靶标某些G4 DNA结构的开启发射特性的化合物的例子的原因。但是,这项研究表明,确实有可能开发出此类化合物,并提供有关特定G4 DNA识别和信号传导分子细节的见识,以推动G4生物学的进一步研究。
更新日期:2020-02-18
down
wechat
bug