Negative volume changes of human G-quadruplexes at unfolding

Abstract G-quadruplexes are tetrahelical structures. They are important targets for anti-cancer drugs, since they are situated at crucial positions within the genome. We studied the volumetric properties of the unfolding of three G-quadruplexes in the presence of potassium ion. The unfolding volume changes were determined using high-pressure fluorescence spectroscopy. The c-MYC, KIT, and VEGF sequences unfold with the transition volume of -17, -6 and -18 cm3/mol, respectively. The small magnitude of the unfolding volume of KIT could be explained by its unique structure and the lower amount of void volume. Since the cell interior is highly crowded, the available volume is restricted. Therefore the volumetric changes during the conformational transformations gain biological importance.