The Truncated Human Telomeric Sequence forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K+Solution
Yuxia Liu, Dengfeng Cheng, Min Ge, Weizhen Lin
Chemical Biology and Drug Design
In 80–90% tumor cells, telomerase becomes active and stabilizes the length of telomeres. The formation and stabilization of G-quadruplexes formed from human telomeric sequences have been proved able to inhibit the activity of telomerase, thus human telomeric G-quadruplex structure has become a potential target for the development of cancer therapy. Hence, structure of G-quadruplex formed in K+ solution has been an attractive hotspot for further studies. However, the exact structure of human telomeric G-quadruplex in K+ is extremely controversial, this study provides information for the understanding of different G-quadruplexes. Here, we report that 22nt and 24nt human telomeric sequences form unimolecular hybrid-type mixed parallel/antiparallel G-quadruplex in K+ solution elucidated utilizing Circular Dichroism, Differential Scanning Calorimetry, and gel electrophoresis. Moreover, individual configuration of these two sequences was speculated in this study. The detailed structure information of the G-quadruplex formed under physiologically relevant condition is necessary for structure-based rational drug design.
Circular dichroism, Protein folding, Thermal stability, Biochemistry, Pharmaceutical