The University of Toledo

Project Seed 2012:  Project Summaries University of Toledo Department of Chemistry

Dr. Jared Anderson

http://www.utoledo.edu/nsm/chemistry/people/Webpages/Anderson.html

Developing Extraction Methods for Removing Impurities from Active Pharmaceutical Ingredients

In the pharmaceutical industry today, the presence of genotoxic impurities in active pharmaceutical ingredients is of great concern. Governmental regulation authorities, such as the Food and Drug Administration, have strict levels in which these impurities can be present after synthesis of the drug component. In our laboratory, we seek new methods and techniques to selectively extract and remove these impurities. We utilize a number of extraction and separation techniques and the summer student will gain exposure to all of these as well as learn the importance of quality control and quality assurance as it is related to the purity of pharmaceutical drugs.

Dr. John Bellizzi

http://www.utoledo.edu/nsm/chemistry/people/Webpages/Bellizzi.html

Inhibitors of an Enzyme That Regulates Circadian Rhythms

The daily cycles of physiology and metabolism known as circadian rhythms are important to the maintenance of the body’s normal homeostasis, and disruption of these rhythms is associated with many disease states. Circadian rhythms are generated by molecular clocks that generate daily cycles of gene expression. The frequency of these oscillations is governed by post-translational modifications of key clock proteins, including phosphorylation by the enzyme casein kinase 1. We are pursuing X-ray crystallographic studies of complexes of casein kinase 1 with inhibitors in order to provide insight into how modulation of the enzyme’s function influences circadian period length.

Dr. Amanda Bryant-Friedrich

http://www.utoledo.edu/pharmacy/depts/mbc/faculty-abryant.html

Oxidative Damage to DNA

Oxidative damage to nucleic acids plays an important role in the etiology of many diseases included cancer and age related disorders. Modified nucleic acids have been synthesized which allow for the generation of specific reactive species in nucleic acids at predetermined locations. Through photochemical activation, modified nucleosides and nucleotides will be damaged and their subsequent degradation products determined using chromatographic methods as well as mass spectroscopy. This project is well suited for students with limited research experience.

Dr. Dragan Isailovic

http://www.utoledo.edu/nsm/chemistry/people/Webpages/Isailovic.html

Quantification of Biomolecules by Liquid Chromatography-Mass Spectrometry (LC-MS)

Separation and quantification of biomolecules in complex mixtures is often performed in academic and industrial laboratories by combination of high-performance liquid chromatography (HPLC) and mass spectrometry (MS). The student working on this project will separate and quantify by LC-MS mixtures of peptides and sugars (glycans) that are isolated from biologically important glycoproteins. The project will involve quantification of native and derivatized biomolecules by tandem mass spectrometry (MS/MS) through monitoring of fragments of separated compounds. The LC-MS results obtained will be correlated to results obtained upon separation of compounds and their quantification by ultraviolet-visible (UV-VIS) and/or fluorescence detectors.

Dr. Ron Viola

http://www.utoledo.edu/nsm/chemistry/people/Webpages/Viola.html

Development of Novel Antibiotics

This project involves the use of standard molecular biology techniques to clone and express genes that encode for our antibiotic target enzyme obtained from a variety of different microorganisms.

Dr. Jianglong Zhu

http://www.utoledo.edu/nsm/chemistry/people/Webpages/Zhu.html

Umpolung Reactivity in Stereoselective Synthesis of 2-Deoxy Glycosides

2-Deoxy-sugars, in which the hydroxyl group at C-2 position is replaced by a hydrogen atom, are a class of biologically important carbohydrates that exist in a wide range of potent natural antitumor antibiotics. In this project, we plan to develop an umpolung reactivity-based approach for stereoselective synthesis of 2-deoxy glycosides which involve reactions between 2-deoxy glycosyl lithium species with glycosyl peroxo acceptors.