T-Space at The University of Toronto Libraries >
School of Graduate Studies - Theses >
Please use this identifier to cite or link to this item:
|Title: ||Synthesis of Caseinolytic Protease Agonists Towards the Synthesis of the Natural Acyldepsipeptides|
|Authors: ||Cossette, Michele|
|Advisor: ||Batey, Robert A.|
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.|
|Appears in Collections:||Master|
This item is licensed under a Creative Commons License
Items in T-Space are protected by copyright, with all rights reserved, unless otherwise indicated.