Synthesis of peptide-based small molecule probes to study redox status and protein prenylation.

Abstract

The use of solid phase peptide synthesis to produce molecular probes for chemical biology applications is an efficient and tunable process allowing for the synthesis of tools for a wide range of applications. The modular nature of peptide synthesis makes it relatively simple to change features of a probe to suit whatever needs are necessary. The sidechains of the amino acid building blocks serve as convenient handles for the addition of fluorophores or other tags. In this thesis, peptides are used as building blocks to make a redox probe and several analogues of an internally quenched Ste24p cleavage probe. I also examine the consequences of solid phase synthesis, specifically racemization, when cysteine is the C-terminal residue. The synthesis of the redox probe was modified to improve the ease of its production. The internally quenched Ste24p cleavage probe was applied to show that C-terminal modifications of the probe do not appear to influence the cleavage kinetics of the Ste24p protease.