ORCID Profile
0000-0002-3903-0018
Current Organisations
University of Western Australia
,
Rockefeller University
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Publisher: Wiley
Date: 09-2016
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6DT04534K
Abstract: Two new, potentially chelating NHC ligands are synthesised, characterised and their preliminary catalytic activity in NHC–Pd and NHC–Ru complexes is evaluated.
Publisher: Wiley
Date: 09-2016
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC03945C
Abstract: N -Functionalised multicarbazoles were found to be highly selective towards G-quadruplex DNA in the presence of 250× excess duplex DNA competitor.
Publisher: Oxford University Press (OUP)
Date: 20-04-2020
DOI: 10.1093/NAR/GKAA262
Abstract: Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element of the KRAS promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating KRAS expression, and has spurred interest in structural elucidation studies of the KRAS G-quadruplexes. Here, we report the first high-resolution crystal structure (1.6 Å) of a KRAS G-quadruplex as a 5′-head-to-head dimer with extensive poly-A π-stacking interactions observed across the dimer. Molecular dynamics simulations confirmed that the poly-A π-stacking interactions are also maintained in the G4 monomers. Docking and molecular dynamics simulations with two G4 ligands that display high stabilization of the KRAS G4 indicated the poly-A loop was a binding site for these ligands in addition to the 5′-G-tetrad. Given sequence and structural variability in the loop regions provide the opportunity for small-molecule targeting of specific G4s, we envisage this high-resolution crystal structure for the KRAS G-quadruplex will aid in the rational design of ligands to selectively target KRAS.
Publisher: Wiley
Date: 12-09-2013
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.BIOCHI.2021.07.008
Abstract: Paraspeckles are RNA-protein structures within the nucleus of mammalian cells, capable of orchestrating various biochemical processes. An overexpression of the architectural component of paraspeckles, a long non-coding RNA called NEAT1 (Nuclear Enriched Abundant Transcript 1), has been linked to a variety of cancers and is often associated with poor patient prognosis. Thus, there is an accumulating interest in the role of paraspeckles in carcinogenesis, however there is a limited understanding of how NEAT1 expression is regulated. Here, we demonstrate that both nuclear G-quadruplex (G4) and paraspeckle formation are significantly increased in a human breast cancer cell line compared to non-tumorigenic breast cells. Moreover, we identified and characterized G4-forming sequences within the NEAT1 promoter and demonstrate stabilization of G4 DNA with a G4-stabilizing small molecule results in a significant alteration in both paraspeckle formation and NEAT1 expression. This G4-mediated alteration of NEAT1 at both the transcriptional and post-transcriptional levels was evident in U2OS osteosarcoma cells, MCF-7 breast adenocarcinoma and MDA-MB-231 triple negative breast cancer cells.
No related grants have been discovered for Arnold Ou.