Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Some Derivatives of 1,3-diazaadamantane Strongly Stimulate Strand Exchange Reaction between Short Oligonucleotides
Earlier, we characterized the behavior of HG122 (compound III) in the DNA Strand Exchange Reaction (SER) and found that this 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 of the structure significantly influenced the compounds’ efficacy in accelerating SER. For example, an increase in the compounds’ aliphatic chains lengths considerably enhanced its efficiency in SER stimulation and in the series of compounds presented in the Figure HG188 (compound IV) was eminently 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 twelve derivatives characterized no agents that retard spontaneous SER were 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nature such as Cationic Comb Copolymers (Kim et al.,2003), linker histones (Bocharova et al., 2012), cobalt hexamine (unpublished observation) etc.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.
W.J.Kim, Y.Cato, T.Akaike, A Maruyama (2003).Cationic comb-type copolymers for DNA analysis. Nat. Mater, 2, 815-820.
T.N.Bocharova, E.A.Smirnova, A.A.Volodin(2012). Linker histone H1 stimulates DNA strand exchange between short oligonucleotides retaining high sensitivity to heterology. Biopolymers, 97,4, 229-239.
1Research-technological Center of Organic & Pharmacological Chemistry