title: Rational design of hetero-ring-expanded guanine analogs with enhanced properties for modified DNA building blocks.
abstract: The properties and modes of recognition of physiological DNAs associated with the four natural nucleobases might be extended, in principle, by the design of non-natural nucleobase derivatives. The goal is an expansion of the genetic alphabet, with the possible outcome of producing new DNAs with improved physical or biological properties. In this work, a new series of hetero-ring-expanded guanine analogs are proposed, and their relevant structural characteristics and electronic properties are determined by density functional theory. The stabilities of the decamer DNA duplexes (dn.dC)10 (where n represents the corresponding expanded guanine analog designed here) are also examined, using molecular dynamics. The simulations show that the designed motifs can form stable DNA-like structures. We determined the pairing energies for the Watson-Crick (WC) hydrogen-bonded dimers between the expanded G-analogs and the natural C, and found that the pairing energies are close to those of the natural GC pair. The calculated adiabatic ionization potentials (IPs) of the size-expanded guanine analogs and their base pairs, and the corresponding vertical ionization potentials, show that some are distinctly smaller than the corresponding natural versions. The HOMO-LUMO energy gaps for most of the size-expanded guanine analogs and their WC base pairs are considerably lower than those of the corresponding natural base and base pairs. Thus, the expanded G bases may be considered as DNA genetic motifs, and they may serve as building blocks for potential biological applications and the development of molecular electronic devices.
authors.affiliation: Institute of Theoretical Chemistry, Shandong University, Jinan, 250100, P.R. China.
authors.forename: Jinmei
authors.initials: J
authors.lastname: Zhang
authors.forename: Robert I
authors.initials: RI
authors.lastname: Cukier
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Bu
mesh_terms: D020029:Base Pairing; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008958:Models, Molecular; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D006571:Heterocyclic Compounds; D009692:Nucleic Acid Heteroduplexes; D006147:Guanine; D004247:DNA