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

The effect of amino groups attached at positions 2 and 8 of the hypoxanthin e moiety in the structure, reactivity and stability of DNA duplexes and tri plexes is studied by means of quantum mechanical calculations, as well as e xtended molecular dynamics (MD) and thermodynamic integration (MD/TI) simul ations. Theoretical estimates of the change in Stability related to 2'-deox yguanosine (G) --> 2'-deoxyinosine (I) --> 8-amino-2'-deoxyinosine (8AI) mu tations have been experimentally verified, after synthesis of the correspon ding compounds. An amino group placed at position 2 stabilizes the duplex, as expected, and surprisingly also the triplex. The presence of an amino gr oup at position 8 of the hypoxanthine moiety stabilizes the triplex but, su rprisingly, destabilizes the duplex. The subtle electronic redistribution o ccurring upon the introduction of an amino group on the purine seems to be responsible for this surprising behavior. Interesting 'universal base' prop erties are found for 8AI.