Publication details

Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands

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Year of publication 2015
Type Article in Periodical
Magazine / Source Chemistry - A European Journal
MU Faculty or unit

Central European Institute of Technology

Web DOI: 10.1002/chem.201500743
Field Physical chemistry and theoretical chemistry
Keywords Density functional calculations; DNA; G-quadruplexes; ligand design; nucleobases
Description A new class of quadruplex nucleobases, derived from 3-deazaguanine, has been designed for various applications as smart quadruplex ligands as well as quadruplex-based aptamers, receptors, and sensors. An efficient strategy for modifying the guanine quadruplex core has been developed and tested by using quantum chemistry methods. Several potential guanine derivatives modified at the 3- or 8-position or both are analyzed, and the results compared to reference systems containing natural guanine. Analysis of the formation energies (BLYP-D3(BJ)/def2-TZVPP level of theory, in combination with the COSMO model for water) in model systems consisting of two and three stacked tetrads with Na+/K+ ion(s) inside the internal channel indicates that the formation of structures with 3-halo-3-deazaguanine bases leads to a substantial gain in energy, as compared to the corresponding reference guanine complexes. The results cast light on changes in the noncovalent interactions (hydrogen bonding, stacking, and ion coordination) in a quadruplex stem upon modification of the guanine core. In particular, the enhanced stability of the modified quadruplexes was shown to originate mainly from increased pi–pi stacking. Our study suggests the 3-halo-3-deazaguanine skeleton as a potential building unit for quadruplex systems and smart G-quadruplex ligands.
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