Streamlining the synthesis of folate mimics as potential antifungal agents
Arts and Sciences
Methionine Synthase (MetSyn) is an enzyme that creates the amino acid methionine, which is essential for all organisms. There are key differences between the B12-independent fungal MetSyn enzyme and the B12-dependant mammalian form, especially with regard to the proximity of the two active sites. Taking advantage of these differences, an antifungal drug could be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. As MetSyn is a folate-dependent enzyme, we are currently exploring the synthesis of various pterin-based molecules as these mimic the essential folate substrate. We have developed optimized paths to allow for rapid generation of new folate-mimics and other pterin derivatives. We have expressed the MetSyn enzyme and begun testing these molecules for activity in a fluorescent assay for monitoring MetSyn activity.
Bennett, Zachary; Grumbles, Kassidy; Bockman, Anna; and Pruet, Jeff, "Streamlining the synthesis of folate mimics as potential antifungal agents" (2019). Symposium on Undergraduate Research and Creative Expression (SOURCE). 806.