Physical Sciences and Mathematics Commons^™

Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett

Wayne State University Theses

Abstract

DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS

by

KHALIN NISBETT

May 2017

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Master of Science

Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …

Methodologies For Attaching Polypyridyl Ligands Into Amino Acids And Synthesis And Biological Evaluation Of Novel Light Activated Peptidomimetic Cysteine Protease Inhibitors Caged By Ruii(Bpy)2, Tomasz Respondek

Wayne State University Dissertations

Two separate subjects are described in this dissertation. The first part describes novel methodologies for attaching polypyridyl ligands into unnatural amino acids. The first chapter describes the different possibilities for attaching metal ligands to peptides and their applications as potential imaging and therapeutic agents covered so far in the literature. It is followed in the second chapter by the description of a new method for the construction of metal-peptide conjugates through the use of three unnatural amino acids, and their adaptation to solid phase synthesis. The third chapter describes the synthesis of a novel, "optimal" substrate for the enantioselective alkylation …