Date of Award

2019-01-01

Degree Name

Doctor of Philosophy

Department

Chemistry

Advisor(s)

Mahesh . Narayan

Abstract

Chagas Disease, also known as American Trypanosomiasis, is endemic to Latin American and is gradually making its way to other countries. The disease is caused by Trypanosoma cruzi, a protozoan parasite that causes lesions and inflammation of organs including the heart, esophagus, and colon. Over 30% of people infected will develop heart disease which can be fatal if untreated. While no vaccine is yet available, research is currently being conducted in finding new treatments for the disease. One target is an enzyme that is believed to help the progression of the disease. Cruzain, a cysteine protease expressed as a pro-enzyme, has been a target since it was discovered that inhibition of the enzyme reduces proliferation of the parasite. Current research is targeted on finding small molecule inhibitors that will interact with fully active cruzain. In our study, we describe a bottom-up approach for the arrest of protein folding. The role of the pro-domain in the folding and maturation of the enzyme is studied by comparing oxidative folding of procruzain and cruzain and by identifying structure stabilizing amino acid residues. The result of these studies can provide a novel approach to the development of Anti-Chagistic treatments and may even be useful in combating other protease-dependent diseases.

Language

en

Provenance

Received from ProQuest

File Size

121 pages

File Format

application/pdf

Rights Holder

Veronica Gonzalez

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