G-Quadruplex Formation from H8 Modified Guanosine Derivatives: From Structure to Function

Ying He, Xiaodong Shi*

Department of Chemistry, University of South Florida, Tampa, FL 33620, USA

G-quadruplex (GQ) has been developed extensively over the past decades. It has been reported that GQs could be used in many directions of chemical, material and biological researches, including supramolecular hydrogel, molecular switch and ionophores. To form a controllable G-quadruplex, one general consideration of self-assembly process is the competition between ΔH formed by hydrogen bonding and the ΔS generated from formation of highly organized structure. It is reasonable to assume that structurally more rigid monomer will lead to the formation of more stable G-quartet due to the reduction of conformation flexibility. One general approach to achieve structurally rigid G-monomer is the modification of C-8 position by fixing the sugar syn/anti conformation. However, according to literature, the studies of C-8-modified G-quadruplexes are rare, mainly due to the challenges associated with the substrate synthesis.

Taking advantage of the electron deficiency of 1,2,3-triazole and electron rich guanosine, we designed a triazole substituted guanosine and successfully achieved high fluorescent intensity which can be used in the application of molecular switch. Herein, we report the new synthesis of 8-aryl guanosine and fluorescent active 8-triazole guanosine and their selfassembly property in solid state and in solution. Through cation templation (Mⁿ⁺= Na⁺, K⁺, Ba²⁺, Pb²⁺, Sr²⁺, La³⁺), discrete self-assembled G-quartet structures were formed. Both structurally novel and functional enriched G-quartets are achieved using this new system. Potential applications in molecular sensing and biological target recognition are expected with this new system.