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Title: X-ray characterization of mesophases of human telomeric G-quadruplexes and other DNA analogues

We report that observed in the folds of guanine-rich oligonucleotides, non-canonical G-quadruplex structures are based on G-quartets formed by hydrogen bonding and cation-coordination of guanosines. In dilute 5'-guanosine monophosphate (GMP) solutions, G-quartets form by the self-assembly of four GMP nucleotides. We use x-ray diffraction to characterize the columnar liquid-crystalline mesophases in concentrated solutions of various model G-quadruplexes. We then probe the transitions between mesophases by varying the PEG solution osmotic pressure, thus mimicking in vivo molecular crowding conditions. Using the GMP-quadruplex, built by the stacking of G-quartets with no covalent linking between them, as the baseline, we report the liquid-crystalline phase behaviors of two other related G-quadruplexes: (i) the intramolecular parallel-stranded G-quadruplex formed by the 22-mer four-repeat human telomeric sequence AG3 (TTAG3)3 and (ii) the intermolecular parallel-stranded G-quadruplex formed by the TG(4)T oligonucleotides. Finally, we compare the mesophases of the G-quadruplexes, under PEG-induced crowding conditions, with the corresponding mesophases of the canonical duplex and triplex DNA analogues.
Authors:
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [1] ;  [5]
  1. Univ. of Massachusetts, Amherst, MA (United States). Dept. of Physics
  2. Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Macromolecular Science and Engineering
  3. Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Macromolecular Science and Engineering, Dept. of Biomedical Engineering, Dept. of Radiology, Dept. of Materials Science and Engineering, Comprehensive Cancer Center, Div. of General Medical Sciences and Oncology
  4. Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Macromolecular Science and Engineering, Dept. of Biomedical Engineering, Dept. of Materials Science and Engineering, Dept. of Physics
  5. Univ. of Massachusetts, Amherst, MA (United States). Dept. of Physics; Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Materials Science and Engineering; J. Stefan Institute, Ljubljana (Slovenia). Dept. of Theoretical Physics; Univ. of Ljubljana, Ljubljana (Slovenia). Dept. of Physics, Faculty of Mathematics and Physics
Publication Date:
OSTI Identifier:
1280920
Grant/Contract Number:
SC0008176; SC0008068
Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
10.1038/srep27079
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22), Division of Materials Sciences and Engineering
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES orientational order; helical parameters; guanine tetraplex; crystal-structure; liquid-crystals; condensation; diffraction; triplex