title: Divalent cations and molecular crowding buffers stabilize G-triplex at physiologically relevant temperatures.
abstract: G-triplexes are non-canonical DNA structures formed by G-rich sequences with three G-tracts. Putative G-triplex-forming sequences are expected to be more prevalent than putative G-quadruplex-forming sequences. However, the research on G-triplexes is rare. In this work, the effects of molecular crowding and several physiologically important metal ions on the formation and stability of G-triplexes were examined using a combination of circular dichroism, thermodynamics, optical tweezers and calorimetry techniques. We determined that molecular crowding conditions and cations, such as Na(+), K(+), Mg(2+) and Ca(2+), promote the formation of G-triplexes and stabilize these structures. Of these four metal cations, Ca(2+) has the strongest stabilizing effect, followed by K(+), Mg(2+), and Na(+) in a decreasing order. The binding of K(+) to G-triplexes is accompanied by exothermic heats, and the binding of Ca(2+) with G-triplexes is characterized by endothermic heats. G-triplexes formed from two G-triad layers are not stable at physiological temperatures; however, G-triplexes formed from three G-triads exhibit melting temperatures higher than 37°C, especially under the molecular crowding conditions and in the presence of K(+) or Ca(2+). These observations imply that stable G-triplexes may be formed under physiological conditions.
authors: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin. 300071, P R China [2] Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin. 300071, P R China.
authors: Hong-Xin
authors: HX
authors: Jiang
authors: Department of Chemistry &Biochemistry, Kent State University, Kent, OH 44242, USA.
authors: Yunxi
authors: Y
authors: Cui
authors: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin. 300071, P R China [2] Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin. 300071, P R China.
authors: Ting
authors: T
authors: Zhao
authors: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin. 300071, P R China [2] Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin. 300071, P R China.
authors: Hai-Wei
authors: HW
authors: Fu
authors: Department of Chemistry &Biochemistry, Kent State University, Kent, OH 44242, USA.
authors: Deepak
authors: D
authors: Koirala
authors: Department of Chemistry &Biochemistry, Kent State University, Kent, OH 44242, USA.
authors: Jibin Abraham
authors: JA
authors: Punnoose
authors: 1] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin. 300071, P R China [2] Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin. 300071, P R China.
authors: De-Ming
authors: DM
authors: Kong
authors: Department of Chemistry &Biochemistry, Kent State University, Kent, OH 44242, USA.
authors: Hanbin
authors: H
authors: Mao
mesh_terms: D001483:Base Sequence; D002021:Buffers; D002151:Calorimetry; D002413:Cations, Divalent / Q000737:chemistry*; D002942:Circular Dichroism; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D052898:Optical Tweezers; D044367:Phase Transition; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D002021:Buffers; D002413:Cations, Divalent; D009841:Oligonucleotides; D006147:Guanine