Exceptionally Selective and Tunable Sensing of Guanine Derivatives and Analogues by Structural Complementation in a G-Quadruplex

2016 ◽  
Vol 128 (44) ◽  
pp. 13963-13968 ◽  
Author(s):  
Xin-min Li ◽  
Ke-wei Zheng ◽  
Yu-hua Hao ◽  
Zheng Tan
Keyword(s):  
G Quadruplex ◽  
Guanine Derivatives

scholarly journals Guanine-vacancy–bearing G-quadruplexes responsive to guanine derivatives

2015 ◽  
Vol 112 (47) ◽  
pp. 14581-14586 ◽  
Author(s):  
Xin-min Li ◽  
Ke-wei Zheng ◽  
Jia-yu Zhang ◽  
Hong-he Liu ◽  
Yi-de He ◽  
...  
Keyword(s):  
Dimethyl Sulfate ◽  
Physiological Concentration ◽  
Unique Type ◽  
Cellular Processes ◽  
G Quadruplex ◽  
Guanine Derivatives ◽  
Guanine Base ◽  
Definition Of ◽  
Thermal Melting

G-quadruplex structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and nanodevices. G-quadruplexes are normally composed of four Gn (n ≥ 3) tracts assembled into a core of multiple stacked G-quartet layers. By dimethyl sulfate footprinting, circular dichroism spectroscopy, thermal melting, and photo-cross-linking, here we describe a unique type of intramolecular G-quadruplex that forms with one G2 and three G3 tracts and bears a guanine vacancy (G-vacancy) in one of the G-quartet layers. The G-vacancy can be filled up by a guanine base from GTP or GMP to complete an intact G-quartet by Hoogsteen hydrogen bonding, resulting in significant G-quadruplex stabilization that can effectively alter DNA replication in vitro at physiological concentration of GTP and Mg2+. A bioinformatic survey shows motifs of such G-quadruplexes are evolutionally selected in genes with unique distribution pattern in both eukaryotic and prokaryotic organisms, implying such G-vacancy–bearing G-quadruplexes are present and play a role in gene regulation. Because guanine derivatives are natural metabolites in cells, the formation of such G-quadruplexes and guanine fill-in (G-fill-in) may grant an environment-responsive regulation in cellular processes. Our findings thus not only expand the sequence definition of G-quadruplex formation, but more importantly, reveal a structural and functional property not seen in the standard canonical G-quadruplexes.

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