Logo for University of Iowa Health Care This logo represents the University of Iowa Health Care

Sondra Dean

Mentor: Michael Ashley Spies, PhD

Year Entered Into Program: 2013

MS Institution: University of Iowa, 2016

Affiliations

  • Medicinal and Natural Products Chemistry

Research Description

One of the greatest public health concerns today is the development of antibiotic resistant pathogenic bacterial strains. In the United States alone, these bacteria infect over 2 million people and are responsible for the death of over 23,000 people every year. This places an urgent need on the discovery and development of antibiotics against novel targets. To date, immensely successful targets have been involved in peptidoglycan biosynthesis with over 60% of antibiotics inhibiting this process. The peptidoglycan layer is a vital component of the cellular envelope of both gram-negative and gram-positive bacteria. If any portion of this layer is improperly formed, the integrity of the entire peptidoglycan may be compromised and the cell will lyse and die. It is formed by chains of N-acetylglucosamine and N-acetylmuramic acid in an alternating pattern that are cross-linked by peptide chains extending from each N-acetylmuramic acid. Glutamate racemase is an enzyme involved in peptidoglycan biosynthesis and is the drug target of interest in my research. It is responsible for generating the D-glutamate component of the peptide chains. Currently, there are no glutamate racemase drugs on the market, making it an attractive target in the fight against antibiotic resistance. The primary focus of my research on this target is to extend the computational approaches of docking and molecular dynamic simulations to structure-based drug design against glutamate racemase isozymes of highly pathogenic species (e.g., E. coli, B. anthracis, and H. pylori).

Awards

  • NIH T32 Predoctoral Fellowship in Pharmacological Sciences (GM067795), University of Iowa, 2015-2016
  • Institutional fellowship support of Training Grant in Pharmacological Sciences (NIH T32 GM067795), University of Iowa, 2014-2015
  • Medicinal and Natural Products Chemistry Fellowship, University of Iowa 2013-2014

Publications

  1. Dean SF, Whalen KL and Spies MA.:  Biosynthesis of a Novel Glutamate Racemase Containing a Site-Specific 7- Hydroxycoumarin Amino Acid: Enzyme-Ligand Promiscuity Revealed at the Atomistic Level., ACS Central Science, 1:364-373, 2015.  PMCID: PMC4626791

Research