Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma

14-3-3σ is an acidic homodimer protein with more than one hundred different protein partners associated with oncogenic signalling and cell cycle regulation. Previous studies have shown that 14-3-3σ functions as a potential tumour suppressor and its expression is commonly downregulated in many types...

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Main Author:	Jabal, Ghazi Ahmad Al
Format:	Thesis
Language:	English
Published:	2023
Subjects:	RS1-441 Pharmacy and materia medica
Online Access:	http://eprints.usm.my/60385/1/GHAZI%20AHMAD%20AL%20JABAL%20-%20TESIS24.pdf
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id	my-usm-ep.60385
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spelling	my-usm-ep.603852024-04-17T08:58:40Z Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma 2023-09 Jabal, Ghazi Ahmad Al RS1-441 Pharmacy and materia medica 14-3-3σ is an acidic homodimer protein with more than one hundred different protein partners associated with oncogenic signalling and cell cycle regulation. Previous studies have shown that 14-3-3σ functions as a potential tumour suppressor and its expression is commonly downregulated in many types of cancer including nasopharyngeal carcinoma (NPC). As the monomers are generally more prone to degradation than dimers, it was hypothesised that a homodimer stabiliser can potentially decrease the degradation of 14-3-3σ. Also, as the 14-3-3σ requires homodimer form to be functionally active, a homodimer stabiliser is expected to also enhance the activity of the 14-3-3σ. However, to date, there is no reported ligand that can bind to the 14-3-3σ dimer interface cavity and stabilise its homodimeric form. Thus, the aim of this study is to identify a potential novel 14-3-3σ homodimer stabiliser. Three different approaches were implemented to identify a potential novel 14-3-3σ homodimer stabiliser, i.e., in silico virtual screening of a commercially available database, searching the literature for compounds reported to target the dimer interface of other 14-3-3 isoforms, and rational design of potentially novel 14-3-3σ homodimer stabilisers. In silico molecular docking and molecular dynamic (MD) simulation with various analysis tools were implemented for the identification of the potential 14-3-3σ homodimer stabiliser 2023-09 Thesis http://eprints.usm.my/60385/ http://eprints.usm.my/60385/1/GHAZI%20AHMAD%20AL%20JABAL%20-%20TESIS24.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Pengajian Sains Farmasi
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RS1-441 Pharmacy and materia medica
spellingShingle	RS1-441 Pharmacy and materia medica Jabal, Ghazi Ahmad Al Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma
description	14-3-3σ is an acidic homodimer protein with more than one hundred different protein partners associated with oncogenic signalling and cell cycle regulation. Previous studies have shown that 14-3-3σ functions as a potential tumour suppressor and its expression is commonly downregulated in many types of cancer including nasopharyngeal carcinoma (NPC). As the monomers are generally more prone to degradation than dimers, it was hypothesised that a homodimer stabiliser can potentially decrease the degradation of 14-3-3σ. Also, as the 14-3-3σ requires homodimer form to be functionally active, a homodimer stabiliser is expected to also enhance the activity of the 14-3-3σ. However, to date, there is no reported ligand that can bind to the 14-3-3σ dimer interface cavity and stabilise its homodimeric form. Thus, the aim of this study is to identify a potential novel 14-3-3σ homodimer stabiliser. Three different approaches were implemented to identify a potential novel 14-3-3σ homodimer stabiliser, i.e., in silico virtual screening of a commercially available database, searching the literature for compounds reported to target the dimer interface of other 14-3-3 isoforms, and rational design of potentially novel 14-3-3σ homodimer stabilisers. In silico molecular docking and molecular dynamic (MD) simulation with various analysis tools were implemented for the identification of the potential 14-3-3σ homodimer stabiliser
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Jabal, Ghazi Ahmad Al
author_facet	Jabal, Ghazi Ahmad Al
author_sort	Jabal, Ghazi Ahmad Al
title	Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma
title_short	Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma
title_full	Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma
title_fullStr	Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma
title_full_unstemmed	Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma
title_sort	identification of novel 14-3-3 sigma homodimer stabiliser in nasopharyngeal carcinoma
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Farmasi
publishDate	2023
url	http://eprints.usm.my/60385/1/GHAZI%20AHMAD%20AL%20JABAL%20-%20TESIS24.pdf
_version_	1804888927363923968

Identification Of Novel 14-3-3 Sigma Homodimer Stabiliser In Nasopharyngeal Carcinoma

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