Master of Chemical Sciences Capstone Projects

Date of this Version

8-11-2017

Document Type

Capstone Report

Abstract

Peptide synthesis and modification is a versatile chemical biology strategy to construct probes and sensors of a variety of types of biological activity, including protein/protein interactions, protein localization, and proteolysis. In my thesis work, I have made probes for three distinct biological applications. To do so, I have used a combination of solid phase peptide synthesis (SPPS), native chemical ligation (NCL), protein expression, and S-alkylation to construct probes with desired functional groups, while minimizing the perturbation to the native structure. In the first project, I constructed photo-crosslinking probes to study the difference in protein-protein interactions of N-terminal acetylated (N-ac) histone H4 peptide versus non-acetylated histone H4 peptide. One protein was identified by Western blot with binding preference to N-Ace histone H4 peptide. In the second separate project, I constructed probes to study the toxicity mechanism of proline/arginine dipeptide PRx from amyotrophic lateral sclerosis (ALS) associated gene C9ORF72. The preliminary result suggested the PRx peptide toxicity on proteasome depends on the length of the (PR)x peptide. In the third project, I synthesized fluorescence sensors to study the positional effects of thioamide on the proteolysis process of chymotrypsin. From hydrolysis studies, my coworkers and I determined that thioamide incorporation at the P1 or P2 positions can greatly inhibit chymotrypsin proteolysis.

Keywords

solid phase peptide synthesis, histone, ALS, thioamide, SPPS, probe, click reaction

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Available for download on Monday, August 05, 2019

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Date Posted: 26 January 2018