title: The Truncated Human Telomeric Sequence forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K(+) Solution.
abstract: 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.
authors: Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 Jialuo Road, Shanghai, 201800, China.
authors: Yuxia
authors: Y
authors: Liu
authors: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Shanghai Institute of Medical Imaging, 180 Fenglin Road, Shanghai, 200032, China.
authors: Dengfeng
authors: D
authors: Cheng
authors: Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 Jialuo Road, Shanghai, 201800, China.
authors: Min
authors: M
authors: Ge
authors: Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 Jialuo Road, Shanghai, 201800, China.
authors: Weizhen
authors: W
authors: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D015195:Drug Design; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D008970:Molecular Weight; D063347:Native Polyacrylamide Gel Electrophoresis; D011089:Polydeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D012995:Solubility; D019098:Telomerase / Q000737:chemistry / Q000378:metabolism; D059506:Telomere Shortening
chemical_list: D000970:Antineoplastic Agents; D011089:Polydeoxyribonucleotides; D012964:Sodium; D019098:Telomerase; D011188:Potassium
keywords: Circular Dichroism; G-quadruplex; anticancer drug; differential scanning calorimetry; telomerase; telomeric DNA