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Modified Guanines as Constituents of Smart Ligands for Nucleic Acid Quadruplexes
Author(s) -
Durec Matúš,
Zaccaria Francesco,
Fonseca Guerra Célia,
Marek Radek
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601608
Subject(s) - guanine , chemistry , stacking , natural bond orbital , nucleic acid , hydrogen bond , g quadruplex , homo/lumo , ligand (biochemistry) , computational chemistry , stereochemistry , crystallography , dna , density functional theory , molecule , biochemistry , nucleotide , organic chemistry , receptor , gene
Repetitive guanine‐rich nucleic acid sequences play a crucial role in maintaining genome stability and the cell life cycle and represent potential targets for regulatory drugs. Recently, it has been demonstrated that guanine‐based ligands with a porphyrin core can be used as markers of G‐quadruplex assemblies in cell tissues. Herein, model systems of guanine‐based ligands are explored by DFT methods. The energies of formation of modified guanine tetrads and those of modified tetrads stacked on the top of natural guanine tetrads have been calculated. The interaction energy has been decomposed into contributions from hydrogen bonding, stacking, and ion coordination and a twist–rise potential energy scan has been performed to find the individual local minima. Energy decomposition analysis reveals the impact of various substituents (F, Cl, Br, I, Me, NMe 2 ) on individual energy terms. In addition, cooperative reinforcement in forming the modified and stacked tetrads, as well as the frontier orbitals participating in the hydrogen‐bonding framework involving the HOMO–LUMO gap between the occupied σ HOMO on the proton‐accepting C=O and =N− groups and unoccupied σ LUMO on the N−H groups, has been studied. The investigated systems are demonstrated to have a potential in ligand development, mainly due to stacking enhancement compared with natural guanine, which is used as a reference.