Exploring the spliceosome using hinokiflavone based probes

Kreinin, Helmi (2018) Exploring the spliceosome using hinokiflavone based probes. PhD thesis, University of Glasgow.

Due to Embargo and/or Third Party Copyright restrictions, this thesis is not available in this service.
Printed Thesis Information: https://eleanor.lib.gla.ac.uk/record=b3301632

Abstract

The spliceosome is the cellular machinery involved in producing mature messenger RNA from pre-mRNA before it is translated into protein by the cells. Improved understanding of this vital cellular process would allow us to design better drugs to combat diseases that depend on splicing mismanagement. Small molecules that affect splicing would be useful in furthering our understanding of this complex cellular mechanism. Hinokiflavone, a biflavonoid natural product, was found to affect splicing in cells. In this work we describe the total synthesis of hinokiflavone, after exploring alternative synthetic routes. Several different series of hinokiflavone analogues were also designed and three of these structural analogues displayed the same bioactivity as hinokiflavone. Various biological assays in which hinokiflavone and the analogues were active were then examined. It was found that these molecules modulate splicing by inhibiting SENP activity. The SENP enzyme removes SUMO, a post-translational modification involved in the cellular control over splicing, hence its inhibition has a marked effect on cellular metabolism.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: biflavonoid, natural product, spliceosome, total synthesis, analogues, SENP inhibitor, SUMO accumulation.
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Supervisor's Name: Hartley, Professor Richard C.
Date of Award: 2018
Embargo Date: 26 January 2022
Depositing User: Miss Helmi Kreinin
Unique ID: glathesis:2018-8705
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 29 Jan 2018 10:44
Last Modified: 15 Jun 2021 09:23
Thesis DOI: 10.5525/gla.thesis.8705
URI: http://theses.gla.ac.uk/id/eprint/8705

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