Item – Theses Canada

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OCLC number
1019492655
Link(s) to full text
LAC copy
Author
Cossette, Michele.
Title
Synthesis of Caseinolytic Protease Agonists Towards the Synthesis of the Natural Acyldepsipeptides.
Degree
M. Sc. -- University of Toronto, 2010
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, 2012.
Description
1 online resource
Notes
Includes bibliographical references.
Abstract
<?Pub Inc> Caseinolytic protease (ClpP) is a cylindrical protease forming the core of protein degradation machinery in eubacteria. ClpP is tightly regulated and is nonfunctional 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.
ISBN
9780494765340
0494765348
9780494765340