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University of Minnesota Department of Chemistry and Biochemistry
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Friday , April 18 2014; 3:00 p.m.; Chem 200

 

Garrett Stoddard

Master Student, Department of Chemistry & Biochemistry, University of Minnesota Duluth

Research Advisor - Dr. Steve Berry

Presents:

“Phenoxazinone Synthase (PHS) Activity of Azurin Variants”

 

Phenoxazinone synthase (PHS) is a multicopper oxidase that catalyzes the oxidation of ortho-aminophenol to aminophenoxazinone, by coupling the 6 e- oxidation with the reduction of O2 (1).  To study this reaction, an azurin model was used.  Our models contain the naturally occurring T1 copper center (see figure, PDB: 4AZU), and an additional designed surface T2 copper center.  The T2 copper centers in these variants were modeled after 2 other naturally occurring copper oxidoreductases, nitrite reductase (NiR) and peptidylglycine α-hydroxylating monooxygenase (PHM) (2).  A PHS activity assay was adapted to investigate the activities of PHM-Azurin and NiR-Azurin using an already 2 e- reduced peroxide shunt pathway (3) as well as the native O2 as oxidants. Optimization of pH and peroxide conditions will be reported along with preliminary Michaelis Menten kinetics for the T2 azurin variants.

 

Michael Williams

Master Student, Department of Chemistry & Biochemistry, University of Minnesota Duluth

Research Advisor - Dr. Venkatram Mereddy

Presents:

"Synthesis and Evaluation of Novel Glycolysis Inhibitors for Cancer Therapy"

 

With so many forms of cancer prevalent and this persistent detrimental disease remaining static new drug targets along with novel small molecules are in dire need for treatment. The targeting of key glycolytic and cell signaling proteins that are over expressed in cancer cells are in the main spotlight in many cancer therapeutics. With enhanced research in this area new small molecules are surfacing that have activity against many types of cancer. Although many pharmaceutical templates are quite different most kinase inhibitor classes of drugs and surface protein inhibitors contain a phenyl urea side group, an important pharmacophore found in many examples alike. Several FDA approved medications such as Sorafenib have exhibited multi targeted activity against advanced renal cell carcinoma and advanced primary liver cancer. In addition many indazole based drugs such as Lonidamine a derivative of indazole-3-carboxylic acid, inhibits aerobic glycolysis in cancer cells which enhances aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. These molecules have different mechanisms and targets but work by targeting VEGFR2, PDGFαβ, and Hexokinase 2 proteins. In this regard, we have designed and synthesized numerous small molecules as multi-targeting inhibitors of tumor glycolysis and also signal transduction. These compounds were characterized and evaluated through biological testing. In this seminar the results of an extensive biological study will be revealed showing the effects of these molecules against human VEGFR2, PDGFαβ, and Hexokinase 2.  Results of cancer cell based cytotox assays of MCF-7, MDA-231, and LNCaP will also be included. To conclude current in vivo mice models and cytotox testing results will be discussed along with future aims.

 

 

Anika Rannikko

Master Student, Department of Chemistry & Biochemistry, University of Minnesota Duluth

Research Advisor - Dr. Anne Hinderliter

Presents:

“The Effect of Annexin a5 Interactions with Lipids in the Membrane”