Small molecule inhibitors of the endoplasmic reticulum associated degradation pathway.

  • Morounfolu Fagbure

Student thesis: Master of Philosophy


Proteins are fundamental components of living organisms. They are synthesised as linear chains of amino acids that must be folded into correct conformation in order to be functional. Ubiquitination is a reversible process that determines protein stability and the removal of ubiquitin is catalysed by deubiquitinating enzymes (DUBs).In this study, various DUBs inhibitors based on specific pharmacophore found in prostaglandins for example, b-AP15 were synthesised. And the aim was to attach the left hand planar domain of ESI so that the DUB inhibitory group would be targeted to the ER. The biological activity of the compounds was assessed by measuring their ability to induce the accumulation of polyubiquitinated proteins in HeLa cells. The results indicate that a fluorinated aromatic moiety is required for the accumulation of polyubiquitinated proteins: compounds synthesised without the fluorine functionality were not able to induce accumulation high molecular weight polyubiquitinated proteins.
Date of Award31 Dec 2012
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorRoger Whitehead (Supervisor)

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