Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/104269
Title: Sugar-modified G-quadruplexes : effects of LNA-, 2'F-RNA- and 2'F-ANA-guanosine chemistries on G-quadruplex structure and stability
Authors: Phan, Anh Tuân
Li, Zhe
Lech, Christopher Jacques
Keywords: DRNTU::Science::Chemistry
Issue Date: 2013
Source: Li, Z., Lech, C. J., & Phan, A. T. (2014). Sugar-modified G-quadruplexes: effects of LNA-, 2'F-RNA- and 2'F-ANA-guanosine chemistries on G-quadruplex structure and stability. Nucleic Acids Research, 42(6), 4068-4079.
Series/Report no.: Nucleic acids research
Abstract: G-quadruplex-forming oligonucleotides containing modified nucleotide chemistries have demonstrated promising pharmaceutical potential. In this work, we systematically investigate the effects of sugar-modified guanosines on the structure and stability of a (4+0) parallel and a (3+1) hybrid G-quadruplex using over 60 modified sequences containing a single-position substitution of 2′-O-4′-C-methylene-guanosine (LNAG), 2′-deoxy-2′-fluoro-riboguanosine (FG) or 2′-deoxy-2′-fluoro-arabinoguanosine (FANAG). Our results are summarized in two parts: (I) Generally, LNAG substitutions into ‘anti’ position guanines within a guanine-tetrad lead to a more stable G-quadruplex, while substitutions into ‘syn’ positions disrupt the native G-quadruplex conformation. However, some interesting exceptions to this trend are observed. We discover that a LNAG modification upstream of a short propeller loop hinders G-quadruplex formation. (II) A single substitution of either FG or FANAG into a ‘syn’ position is powerful enough to perturb the (3+1) G-quadruplex. Substitution of either FG or FANAG into any ‘anti’ position is well tolerated in the two G-quadruplex scaffolds. FANAG substitutions to ‘anti’ positions are better tolerated than their FG counterparts. In both scaffolds, FANAG substitutions to the central tetrad layer are observed to be the most stabilizing. The observations reported herein on the effects of LNAG, FG and FANAG modifications on G-quadruplex structure and stability will enable the future design of pharmaceutically relevant oligonucleotides.
URI: https://hdl.handle.net/10356/104269
http://hdl.handle.net/10220/19559
ISSN: 0305-1048
DOI: 10.1093/nar/gkt1312
Rights: © The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Journal Articles

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