Covalent binding of a bridged pyridinium aldehyde with the self-complementary decamer [d(ATGACGTCAT)]2. Gel analysis, MALDI mass spectrometry and NMR studies

Abstract

Gel analysis, MALDI-TOF mass spectrometry and NMR spectroscopy show that a tethered pyridinium aldehyde, from a new class of DNA-interacting agents, binds to the self-complementary [d(ATGACGTCAT)]₂ decamer. The reaction proceeds via a two-step pathway: fast non-covalent outside association (complex formation) is followed by slow covalent addition (adduct formation) upon temperature increase. Both interactions occur mainly at the central CpG in the oligonucleotide, the latter leading finally to the reversible formation of an aminal through nucleophilic attack of the exocyclic guanine amino group in the minor groove of the helix.