Submission Date

7-20-2024

Document Type

Paper- Restricted to Campus Access

Department

Chemistry

Faculty Mentor

Julianne M. Yost

Comments

Presented during the 26th Annual Summer Fellows Symposium, July 19, 2024 at Ursinus College.

Project Description

Methyltransferases are a class of enzymes which are responsible for the transfer of methyl groups to DNA, histones, and other protein targets. DNA and protein methylation are common post-translational modifications in eukaryotic cells and play a significant role in many biological pathways. The overexpression of certain methyltransferases has been implicated in multiple types of cancer, cardiovascular diseases, and neurodegenerative disorders making them promising therapeutic targets. Thus, a potent and selective inhibitor has the potential to aid in future drug discovery efforts. This work focused on finalizing a library of potential inhibitors, which will then be tested for biological activity against several methyltransferases. In this study, we utilized a two-step synthesis from commercially available starting materials involving reductive amination and a recently optimized deprotection reaction to obtain the desired compounds. We expanded on our previous work by showing that the optimized deprotection method could be applied to substituted compounds without significant decomposition or byproduct formation. This work also explored HPLC conditions for the characterization and eventual purification of our synthesized molecules. The collective inhibitory activities of the compounds in our small molecule library will provide useful structure-activity relationship information for different methyltransferases.

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