Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/140171
Title: Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides
Authors: Winnerdy, Fernaldo Richtia
Das, Poulomi
Heddi, Brahim
Phan, Anh Tuân
Keywords: Science::Chemistry
Issue Date: 2019
Source: Winnerdy, F. R., Das, P., Heddi, B., & Phan, A. T. (2019). Solution structures of a G-quadruplex bound to linear- and cyclic-dinucleotides. Journal of the American Chemical Society, 141(45), 18038-18047. doi:10.1021/jacs.9b05642
Project: NRF-NRFI2017-09
Journal: Journal of the American Chemical Society
Abstract: Cyclic dinucleotides have emerged as important secondary messengers and cell signaling molecules that regulate several cell responses. A guanine-deficit G-quadruplex structure formation by a sequence containing (4n – 1) guanines, n denoting the number of G-tetrad layers, was previously reported. Here, a (4n – 1) G-quadruplex structure is shown to be capable of binding guanine-containing dinucleotides in micromolar affinity. The guanine base of the dinucleotides interacts with a vacant G-triad, forming four additional Hoogsteen hydrogen bonds to complete a G-tetrad. Solution structures of two complexes, both comprised of a (4n – 1) G-quadruplex structure, one bound to a linear dinucleotide (d(AG)) and the other to a cyclic dinucleotide (cGAMP), are solved using NMR spectroscopy. The latter suggests sufficiently strong interaction between the guanine base of the dinucleotide and the vacant G-triad, which acts as an anchor point of binding. The binding interfaces from the two solution structures provide useful information for specific ligand design. The results also infer that other guanine-containing metabolites of a similar size have the capability of binding G-quadruplexes, potentially affecting the expression of the metabolites and functionality of the bound G-quadruplexes.
URI: https://hdl.handle.net/10356/140171
ISSN: 0002-7863
DOI: 10.1021/jacs.9b05642
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jacs.9b05642
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Journal Articles

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