128 Some derivatives of 1,3-diazaadamantane strongly stimulate strand exchange reaction between short oligonucleotides

Abstract

Earlier, we characterized the behavior of HG122 (compound III) in the DNA Strand Exchange Reaction (SER) and found that 1,3-diazaadamantane derivative facilitates SER in the system of short oligonucleotides (Gabrielian et al., 2011). In the present study, a series of new derivatives of 1,3-diazaadamantane have been synthesized with the purpose to discern how small variations in the compound structure can influence its activity in SER and try to get more effective substances for stimulation of SER. We revealed that most of the small variations in the structure significantly influenced the compounds’ efficacy in accelerating SER. For example, an increase in the compounds’ aliphatic chain lengths considerably enhanced its efficiency in SER stimulation and in the series of compounds presented in the Figure HG188 (compound IV) was eminently the most potent agent in the stimulation of SER. Small modifications in other parts of the 1,3-diazaadamantane molecule also influenced the SER stimulation and several derivatives more efficient in facilitating SER than HG122 were revealed. Some of the compounds exhibited virtually negligible capability to stimulate SER but, interestingly, out of 12 derivatives characterized, agents that retard spontaneous SER were not found. Earlier, the stimulation of the DNA strand exchange was documented for different ligands of the policationic nature such as Cationic Comb Copolymers (Kim et al., 2003), linker histones (Bocharova et al., 2012), cobalt hexamine (unpublished observation) etc. The present results provide us with a novel class of SER facilitating compounds – the cationic amphiphiles that can serve as interesting objects for further understanding of different aspects of DNA SER. Biomedical implications and prospects in biomedical applications of these and similar compounds’ activity in SER remain to be investigated.