title: A parallel stranded G-quadruplex composed of threose nucleic acid (TNA).
abstract: G-rich sequences can adopt four-stranded helical structures, called G-quadruplexes, that self-assemble around monovalent cations like sodium (Na+) and potassium (K+). Whether similar structures can be formed from xeno-nucleic acid (XNA) polymers with a shorter backbone repeat unit is an unanswered question with significant implications on the fold space of functional XNA polymers. Here, we examine the potential for TNA (α-l-threofuranosyl nucleic acid) to adopt a four-stranded helical structure based on a planar G-quartet motif. Using native polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) and solution-state nuclear magnetic resonance (NMR) spectroscopy, we show that despite a backbone repeat unit that is one atom shorter than the backbone repeat unit found in DNA and RNA, TNA can self-assemble into stable G-quadruplex structures that are similar in thermal stability to equivalent DNA structures. However, unlike DNA, TNA does not appear to discriminate between Na+and K+ions, as G-quadruplex structures form equally well in the presence of either ion. Together, these findings demonstrate that despite a shorter backbone repeat unit, TNA is capable of self-assembling into stable G-quadruplex structures.
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, CA, 92697.
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Liao
authors.affiliation: School of Molecular Sciences and the Biodesign Institute, Arizona State University. Tempe, AZ, 85287.
authors.forename: Irina
authors.initials: I
authors.lastname: Anosova
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, CA, 92697.
authors.forename: Saikat
authors.initials: S
authors.lastname: Bala
authors.affiliation: School of Molecular Sciences and the Biodesign Institute, Arizona State University. Tempe, AZ, 85287.
authors.forename: Wade D
authors.initials: WD
authors.lastname: Van Horn
authors.affiliation: Department of Pharmaceutical Sciences, University of California, Irvine, CA, 92697.
authors.forename: John C
authors.initials: JC
authors.lastname: Chaput
mesh_terms: D002942:Circular Dichroism; D054856:G-Quadruplexes; D009682:Magnetic Resonance Spectroscopy; D063347:Native Polyacrylamide Gel Electrophoresis; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D013780:Tetroses / Q000737:chemistry*
chemical_list: D009696:Nucleic Acids; D009841:Oligonucleotides; D013780:Tetroses; C073321:erythrose
keywords: quadruplex; synthetic genetics; xeno-nucleic acids