The acridine ring selectively intercalated into a DNA helix at various types of abasic sites: double strand formation and photophysical properties

Abstract

The interactions between the intercalating agent and the three types of abasic sites: abasic frameshift, apurinic and apyrimidinic, were investigated. 9-amino-6-chloro-2-methoxyacridine (ACMA), whose spectroscopic properties are strongly perturbed by the environment, was selected as the intercalating agent. The optically pure threoninol derived from the reduction of L-threonine was used as an artificial abasic site mimicking the ring-opened natural ribose. In order to secure the selective intercalation to the adjacent abasic site, ACMA and the abasic site were connected through a tri- pentamethylene linker. These modified oligonucleotides covalently linked to an ACMA molecule at the internucleotide site having the same base-sequence were synthesized using the acridine-phosphoramidites. Although all the modified oligonucleotides lack a nucleobase at the intervening position, these double strands showed high thermal stability. The pentamethylene linker and the apyrimidinic systems were especially stabilized. At the same time, sharpness of the absorption spectra and a new fluorescent band of the acridine, due to the fixation of the environment around ACMA, were observed. Therefore, it is concluded that the acridine binds preferentially to the apyrimidinic site rather than the frameshift abasic site and that the surroundings of the acridine are strictly fixed at the microenvironmental level.