test Browse by Author Names Browse by Titles of Works Browse by Subjects of Works Browse by Issue Dates of Works
       

Advanced Search
Home   
 
Browse   
Communities
& Collections
  
Issue Date   
Author   
Title   
Subject   
 
Sign on to:   
Receive email
updates
  
My Account
authorized users
  
Edit Profile   
 
Help   
About T-Space   

T-Space at The University of Toronto Libraries >
School of Graduate Studies - Theses >
Master >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/30145

Title: Synthesis of Caseinolytic Protease Agonists Towards the Synthesis of the Natural Acyldepsipeptides
Authors: Cossette, Michele
Advisor: Batey, Robert A.
Department: Chemistry
Keywords: Chemistry
Medicinal chemistry
ClpP
depsipeptide
antibiotic
caseinolytic protease
ACP
Activators of Self-Compartmentalizing Proteases
Issue Date: 30-Nov-2011
Abstract: Caseinolytic protease (ClpP) is a cylindrical protease forming the core of protein degradation machinery in eubacteria. ClpP is tightly regulated and is non-functional without a member of the Clp-ATPases. A new class of antibiotics, termed ADEPs, bind to ClpP and allow for activation without the Clp-ATPases; leading to cell death. A more efficient synthetic route to the ADEPs utilizing solid-phase peptide synthesis was investigated. A linear peptide was synthesized, however attempts to close the depsipeptidic macrocycle via macrolactonization failed. Further attempts of assembling a branched depsipeptide for ring closure via a macrolactamization resulted in products that were not stable to cleavage conditions. A group of molecules termed Activators of Self-Compartmentalizing Proteases (ACP) were identified through a screen for activity towards ClpP. Compound ACP1 was synthesized along with twelve analogs and their activity towards ClpP evaluated. The project resulted in a compound with a higher activity than its natural product counterpart.
URI: http://hdl.handle.net/1807/30145
Appears in Collections:Master

Files in This Item:

File Description SizeFormat
Cossette_Michele_S_201011_MSc_thesis.pdf10 MBAdobe PDF
View/Open

This item is licensed under a Creative Commons License
Creative Commons

Items in T-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

uoft