DEVELOPMENT OF UNNATURAL SUBSTRATES AND TRYPTOPHAN AMINO ACIDS TO STUDY PROTON COUPLED ELECTRON TRANSFER IN ENZYMES

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Kei Ohgo (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Proton-coupled electron transfer plays an important role in substrate oxidation by C-H bond cleavage and long-range pathways associated with bioenergetics. This thesis is focused on the synthesis of unnatural substrates and tryptophan amino acids to study these effects in enzyme reactions. The functionalization of C-H bonds is an important chemical transformation, representing a challenge in the design of asymmetric organometallic catalysts to generate a range of organic molecules with diverse functional groups. Soybean lipoxygenase-1 is a model enzyme system that catalyzes C-H activation reactions. Unnatural and volume-filling fatty acid derivatives were designed to test with a mutant soybean lipoxygenase that has an expanded active site. The goal of this strategy is to develop new hydroperoxide-based products of long-chain aliphatic compounds. Fluorinated 5-hydroxytryptophan (Fn-5HOW) derivatives were synthesized on a large scale using a chemoenzymatic approach. These redox-active Fn-5HOW derivatives exhibit tyrosine-like proton-bound oxidation and are associated with the spectroscopic characteristics of neutral radicals that are easily distinguishable from natural aromatic amino acids. As a proof of concept, these unnatural amino acids have been incorporated into structured peptides and model proteins. These unnatural fluorinated 5HOW derivatives may act as reporters for tryptophan-mediated biological electron transport.

Additional Information

Publication

Thesis

Language: English

Date: 2020

Keywords

Proton Coupled Electron Transfer, Tryptophan, Lipoxyganses

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