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Access Type

WSU Access

Date of Award

January 2018

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry

First Advisor

Jeremy J. Kodanko

Abstract

Photocaging biologically active molecules hold great promise for providing researchers the ability to target key physiological sites in living organisms. This dissertation focuses on improving the efficacy of cysteine cathepsin inhibitors and on the application of inhibitors to be used in novel combination therapies for cancer. Four research areas pertaining to this dissertation, i) Cysteine cathepsin proteases, ii) Cancer treatment, iii) Phototherapy, and iv) Photocages in biological applications were summarized in the introductory chapter. Next, examination of the effect of the steric bulk on Ru(TPA) complexes is described for improving quantum yield of ligand exchange. It showcased that steric bulk accelerates thermal dissociation along with photodissociation. Also, the result presented here show that the metal complexation ameliorates cysteine cathepsins inhibitor efficiency. Later in this thesis, the synthesis and evaluation of a cysteine cathepsin inhibitor-based drug are reported. The inhibitor showcased promising in vitro results as an effective agent to block aberrant proteases and kill cancer cells effectively. Finally, CA-074, a known cathepsin B inhibitor, was caged using bodipy an organic photocage to convert cell impermeable compounds to cell-permeable pro-drugs.

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