G- and C-rich quadruplex forming DNA sequences contribute to maintaining genome integrity in the case of centromeric and telomeric DNA regions, and to regulation of gene expression in the case of promoter regions of protein coding genes. So far, these non-B DNA structures were shown to be involved in more than 40 pathological human conditions including cancer. As these non-B DNA structures are a valid drug design targets, their physiologically relevant topologies and structural characteristics need to be clearly understood. In this project, we propose systematic investigations of the influence of non-specific physical-chemical factors on structure of DNA quadruplexes. In parallel, we propose characterization of these structures under the physiological conditions in vivo using state-of-the-art method of in-cell NMR spectroscopy. The acquired information will help to identify physiologically relevant structures of G- and C-quadruplexes. This is a prerequisite for improvement of the selectivity of leading (mainly) antitumor compounds that targets these structures and have already entered preclinical or clinical trials. The improvement of selectivity is essential to suppress the side effects caused by nonselective drug binding.

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