Unraveling the Thermodynamics of the Folding and Interconversion of Human Telomere G-Quadruplexes

详细信息    查看全文

• 作者：Dr. Matjaž Bončina ; Prof. Dr. Gorazd Vesnaver ; Prof. Dr. Jonathan Brad Chaires and Prof. Dr. Jurij Lah
• 刊名：Angewandte Chemie International Edition
• 出版年：2016
• 出版时间：August 22, 2016
• 年：2016
• 卷：55
• 期：35
• 页码：10340-10344
• 全文大小：1975K
• ISSN：1521-3773

文摘

Why human telomere DNA fragments fold into different G-quadruplex structures with parallel, hybrid, and antiparallel strand orientations depending on the temperature and concentration of co-solutes remains poorly understood. Similarly, the formation of intermediate structures along the folding or interconversion pathways is not well understood. Herein, we address these questions by introducing a conceptual framework, based on the global thermodynamic analysis of DSC and CD spectroscopy data, which led to a detailed description of the topological phase space (phase diagram) of the stability of the human telomere fragment 5′-AGGG(TTAGGG)₃-3′ (Tel22). This framework clarifies the driving forces of quadruplex folding and interconversion processes over a wide range of temperatures and ion (K⁺, Na⁺) and polyethylene glycol (PEG) concentrations and demonstrates their linkage to the human telomere DNA structural features.