title: The effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine.
abstract: The effect of amino groups attached at positions 2 and 8 of the hypoxanthine moiety in the structure, reactivity and stability of DNA duplexes and triplexes is studied by means of quantum mechanical calculations, as well as extended molecular dynamics (MD) and thermodynamic integration (MD/TI) simulations. Theoretical estimates of the change in stability related to 2'-deoxyguanosine (G) --> 2'-deoxyinosine (I) --> 8-amino-2'-deoxyinosine (8AI) mutations have been experimentally verified, after synthesis of the corresponding compounds. An amino group placed at position 2 stabilizes the duplex, as expected, and surprisingly also the triplex. The presence of an amino group at position 8 of the hypoxanthine moiety stabilizes the triplex but, surprisingly, destabilizes the duplex. The subtle electronic redistribution occurring upon the introduction of an amino group on the purine seems to be responsible for this surprising behavior. Interesting 'universal base' properties are found for 8AI.
authors: Departament de Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Martí i Franques 1, Barcelona 08028, Spain.
authors: E
authors: E
authors: Cubero
authors: R
authors: R
authors: Güimil-García
authors: F J
authors: FJ
authors: Luque
authors: R
authors: R
authors: Eritja
authors: M
authors: M
authors: Orozco
mesh_terms: D001483:Base Sequence; D003198:Computer Simulation; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006860:Hydrogen Bonding; D007288:Inosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D009838:Oligodeoxyribonucleotides; C051802:triplex DNA; D007288:Inosine; D004247:DNA