Unravelling the structural function relationship of DNA secondary structures

Arnold Ou

doi:10.26182/5dbf80d56c6b2

Unravelling the structural function relationship of DNA secondary structures

Arnold Ou

School of Molecular Sciences

Research output: Thesis › Doctoral Thesis

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Abstract

G-quadruplexes or G4s are secondary DNA structures found in the genome. G4s have been implicated in a range of diseases such as cancer. Because of this, G4s are becoming attractive targets for drug therapies, as it has been shown that stabilization of G4s can alter cancer gene expression. In this work, we developed a new family of multicarbazole ligands, which show unprecedented selectivity towards the KRAS G4, a prominent oncogene. Using our obtained crystal structure of the KRAS G4, we performed modeling studies to reveal the unique binding between the KRAS G4 and our ligands.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Smith, Nicole, Supervisor Swaminatha Iyer, Iyer, Supervisor Dorta, Reto, Supervisor
Thesis sponsors	Australian Government Research Training Program
Award date	23 Oct 2019
DOIs	https://doi.org/10.26182/5dbf80d56c6b2
Publication status	Unpublished - 2019

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10.26182/5dbf80d56c6b2

THESIS - DOCTOR OF PHILOSOPHY - OU Arnold - 2019 - Part 1
THESIS - DOCTOR OF PHILOSOPHY - OU Arnold - 2019 - Part 2
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Cite this

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title = "Unravelling the structural function relationship of DNA secondary structures",

abstract = "G-quadruplexes or G4s are secondary DNA structures found in the genome. G4s have been implicated in a range of diseases such as cancer. Because of this, G4s are becoming attractive targets for drug therapies, as it has been shown that stabilization of G4s can alter cancer gene expression. In this work, we developed a new family of multicarbazole ligands, which show unprecedented selectivity towards the KRAS G4, a prominent oncogene. Using our obtained crystal structure of the KRAS G4, we performed modeling studies to reveal the unique binding between the KRAS G4 and our ligands.",

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AB - G-quadruplexes or G4s are secondary DNA structures found in the genome. G4s have been implicated in a range of diseases such as cancer. Because of this, G4s are becoming attractive targets for drug therapies, as it has been shown that stabilization of G4s can alter cancer gene expression. In this work, we developed a new family of multicarbazole ligands, which show unprecedented selectivity towards the KRAS G4, a prominent oncogene. Using our obtained crystal structure of the KRAS G4, we performed modeling studies to reveal the unique binding between the KRAS G4 and our ligands.

KW - G-quadurplexes

KW - G4s

KW - G4-ligands

KW - Gene expression

KW - KRAS G4

KW - Secondary DNA structures

KW - Crystal structures

KW - Sequencing

U2 - 10.26182/5dbf80d56c6b2

DO - 10.26182/5dbf80d56c6b2

M3 - Doctoral Thesis

ER -

Unravelling the structural function relationship of DNA secondary structures

Abstract

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