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The effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine

Posted June 8th, 2010 by pschmidtke
TitleThe effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine
Publication TypeJournal Article
Year of Publication2001
AuthorsCubero, E, Guimil-Garcia R, Luque FJ, Eritja R, Orozco M
JournalNucleic acids research
Volume29
Issue12
Pagination2522 - 2534
Date Published2001/06/15/
KeywordsBase Sequence; Computer Simulation; DNA/chemical synthesis/chemistry/genetics/metabolism; Hydrogen Bonding; Inosine/chemistry/genetics/metabolism; Models, Molecular; Molecular Structure; Mutation; Nucleic Acid Conformation; Nucleic Acid Denaturation; Oligodeoxyribonucleotides/chemical synthesis/chemistry/genetics/metabolism; Quantum Theory; Thermodynamics
AbstractThe 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.