Designing a Novel Inhibitor for Cobalamin-Independent Methionine Synthase

Level of Education of Students Involved

Undergraduate

Faculty Sponsor

Jeffrey Pruet

College

College of Arts & Sciences (CAS)

Discipline(s)

Chemistry

ORCID Identifier(s)

0009-0007-3831-6245

Presentation Type

Oral Presentation

Symposium Date

Spring 4-30-2026

Abstract

Microbial infections are some of the leading causes of death and antimicrobial-resistant “superbugs” have become a growing issue. There is a great need to explore new and alternative pathways for fighting these diseases. One method is by exploring Methionine synthase (MetSyn), which plays a critical role in cellular one-carbon metabolism, converting homocysteine to form methionine, a key amino acid required for protein synthesis and methyl group transfer reactions. Key differences between the B12-independant fungal MetSyn enzyme and the B12-dependant mammalian enzyme allow for selective targeting of the fungal enzyme. Inhibition of MetSyn offers a promising strategy for therapeutic and antimicrobial development. The focus of this research is the design, synthesis, and evaluation of a novel inhibitor selective for fungal MetSyn. Computational modeling and molecular docking were used to guide structural optimization of lead compounds. This interdisciplinary approach, integrating computational chemistry, organic synthesis, and quantitative chemistry, aims to elucidate the structure-activity relationships governing MetSyn inhibition. Ultimately, the findings of this project will contribute to the understanding of drug design and may support the development of new antimicrobial agents.

Biographical Information about Author(s)

Damon Virgo is a senior ACS Chemistry major at Valparaiso University with minors in math, physics, and biology. His research focuses on designing inhibitors for cobalamin-independent methionine synthase, combining interests in biochemistry and medicinal chemistry. He has experience in materials science and organic synthesis.

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