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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Cubero E,Güimil-García R,Luque FJ,Eritja R,Orozco M

doi

10.1093/nar/29.12.2522

keywords:

subject

Has Abstract

pub_date

2001-06-15 00:00:00

pages

2522-34

issue

12

eissn

0305-1048

issn

1362-4962

journal_volume

29

pub_type

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