2021 Undergraduate Research Showcase
 

Title

Kinetic Study of Novel Inhibitors Against Giardia duodenalis MTA Nucleosidase

Document Type

Student Presentation

Presentation Date

4-23-2021

Faculty Sponsor

Ken Cornell, Ph.D.

Abstract

Giardia duodenalis is a protozoan parasite that infects the small intestine and causes 1.2 million illnesses in the United States each year, but the even larger concern is in developing countries where there is less access to clean water. In many countries the infection rate of G. duodenalis reaches 50% of the population annually.

Currently, giardiasis is treated with metronidazole, but G. duodenalis is becoming increasingly more resistant to this medication and there are few alternatives, making it vital that novel medical interventions be considered.

A potential target of new drug development is the enzyme 5’-methylthioadenosine nucleosidase (MTN) which cleaves methylthioadenosine (MTA) to adenine and methylthioribose. This pathway is of great interest because inhibiting the cleavage of MTA would disrupt the ability to recover essential compounds such as adenine and methionine, hindering cellular growth.

For this study, recombinant Giardia MTN proteins were purified, and the inhibitory activity of selected small molecule inhibitors tested using an UV spectrophotometric assay. We found that several compounds demonstrate inhibitory activity against Giardia MTN enzymes at low micromolar concentrations, underscoring their potential as new antiparasitic drugs for the treatment of giardiasis.

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