Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 16 of 16 for “"p53-MDM2"”.
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Targeting the p53/MDM2 protein-protein interaction
The p53/MDM2 protein-protein interaction is the most widely characterised proteinprotein interaction to date. As of 2014, there are over 20 compounds that have been shown to the p53-MDM2 protein-protein interaction, however many compounds have not progressed into clinical trials due to their high …
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Engineering a synthetic p53-Mdm2 network in budding yeast
p53 is among the most thoroughly studied proteins to date. Its tumour suppressor activity and the consideration that inactivation of the p53 pathway is a common, if not universal, feature of all human cancers, have gained it the interest of a multitude of researches seeking new therapies against …
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Using Stable Limit Cycles to Model p53-Mdm2 Protein Interactions in the Presence of DNA Damage
The protein p53 is constantly made and destroyed within a cell. Another protein, Mdm2, is a negative regulator of p53. In the presence of DNA damage, Mdm2 does not bind to p53, thus activating the p53 protein. This activation then promotes the mechanisms necessary to either fix or terminate the …
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NONCOVALENT INTERACTION OF PLATINUM PLANAR AMINE COMPOUNDS WITH TRYPTOPHAN: A STRATEGY TO INTERFERE WITH P53-MDM2 INTERACTIONS AND TARGETING RETROVIRAL ZN FINGER-DNA INTERACTION (HIV NCP7)
<p>Non-covalent interactions involving π-π stacking play an essential role in self-assembly and molecular recognition processes such as protein folding and DNA/RNA-protein selective recognition. The knowledge gained from these studies could provide insight into possible site recognition complexes, …
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Mathematical modelling of negative feedback signal transduction processes
… of the Hes1, Hes1-Stat3 and p53-Mdm2 pathways.<br/>In chapter 3, we have undertaken a detailed study of the previous work done in the field. Building on this previous work, we derive mathematicalmodels (systems of partial differential equations) to capture the evolution in …
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Development of orthogonal nanotherapeutics for colorectal cancer treatment
The tumour suppressor p53 has an impressive ability to regulate multiple cellular events such as apoptosis and cell cycle. Strategies aimed at activating the wild-type p53 convene a great therapeutic potential. This led to the discovery of the small molecule inhibitors, MDM2 antagonists which …
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Azobenzenes for the development of therapeutics
… stapling methodology to target the disruption of p53/MDM2 protein-protein interaction. Through competitive fluorescence polarisation, a substantial discrepancy in binding affinity was observed between each isomer for the p53-interacting domain of human MDM2. Chapter 2 explores the applicability of …
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Strain-promoted Stapled Peptides for Inhibiting Protein-protein Interactions
… to the strain promoted double click stapling of p53-based diazido peptides in an effort to generate stapled peptide-based inhibitors of the oncogenic p53 MDM2 PPI, a validated target for anticancer therapeutics. Three stapled peptides were found to have inhibitory activity, thus demonstrating the …
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Development of stapled peptide targeted covalent inhibitors and synthesis of novel ADC payloads for applications in cancer therapy
… peptide–targeted covalent inhibitors (SPTCIs) of p53–MDM2 protein–protein interaction (PPI). Herein, the development and synthesis of three novel electrophilic staples and four stapled peptides are described. The stapled peptides bear moieties to covalently target a surface-exposed lysine residue …
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Phospho-regulation and metastatic potential of Murine Double Minute 2
Murine double minute (Mdm2) is a highly modified and multi-faceted protein that is overexpressed in numerous human malignancies. It engages in many cellular activities and is essential for development since deletion of mdm2 is lethal in early stages of embryonic development. The most studied …
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OMICs based identification of the mechanisms that underpin FAK’s regulation of gene expression
… to a number of transcription factors such as P53, MDM2, IL33, RUNX1 and SP1. These nuclear interactions have been linked to proliferation, survival, differentiation and regulation of the anti-tumour immune response and cell cycle. However, despite these findings, the mechanism by which FAK …
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Characterisation of the role of ING5
The tumour suppressor protein p53 stops cell division by activating the expression of p21WAF1/CIP1, whenever it senses that a cells DNA is damaged. Thus, giving the cell a chance to repair the damaged DNA before its errors are duplicated and passed onto daughter cells. When p53 is mutated, it loses …
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Interlocking mechanisms regulating the circadian clock response to DNA damage
… (PER2) binds to the tumor suppressor protein p53, a key regulatory checkpoint component that modulates cell cycle progression and the cellular response to genotoxic stress. PER2 binding to p53 modulates p53's stability, cellular localization, and transcriptional activity. As described in …
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Therapeutic Efficacy of P53 Restoration In Mdm2-Overexpressing Tumors
<p>The<em> TP53 </em>tumor suppressor is the most mutated gene in human cancers. Recent studies using genetically modified mouse models have shown that restoring the expression of wild-type <em>p53</em> has led to tumor growth suppression in various types of tumors lacking p53. Other mechanisms, …
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Brit1/Mcph1 Mediates The Dna Damage Response By Inducing P53 Stability and Promoting Atr Signaling
… of BRIT1 include a direct interaction with the p53 tumor suppressor protein to promote p53 stability, and binding and recruitment of TopBP1 to sites of replication stress to maintain ATR signaling.</p> <p>The stability of p53 is largely dependent on its negative regulator, the MDM2 ubiquitin E3 …
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Targeting Apoptotic Pathways to Overcome Drug Resistance In Acute Myeloid Leukemia
… to tumorigenesis and drug resistance. BCL-2 and p53 proteins represent two focal nodes in convergent apoptosis signaling. Upregulation of anti-apoptotic BCL-2 family members and inactivation of p53 functions are two canonical approaches exploited by cancer cells to escape apoptosis. In the …