Chemical Methods for Studying the Biosynthesis of Lantibiotics and Prostaglandins

Prostaglandin H Synthase (PGHS) converts arachidonic acid (AA) into the first intermediate in the synthesis of prostaglandins via a radical mechanism. Prostaglandins play a number of roles in the body, including the regulation of blood flow to certain organs, controlling transport across membranes, and the stimulation of inflammation. A tyrosine radical is proposed to initiate the cyclooxygenase reaction by abstraction of the pro-S hydrogen atom at position 13 of AA to form a fatty acid radical, proposed to be a pentadienyl radical. Site-specifically deuterated AAs can contribute to corroboration of the proposed structure, as their reaction with the enzyme should lead to predictable changes in the hyperfine pattern observed in the EPR spectrum. We therefore designed syntheses for and prepared 15-[2H]-AA and four more deuterated compounds as structural probes. The EPR spectra obtained provide strong support for the assignment of the radical signal to a pentadienyl radical.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Okeley, Nicole Marie

Contributors dc:contributor

• van der Donk, Wilfred A.

• Chemistry, Organic

Language dc:language

eng

Identifier

(MiAaPQ)AAI3044191

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84065