Submission Date


Document Type

Paper- Restricted to Campus Access




Julianne M. Yost

Committee Member

Ryan Walvoord

Committee Member

Ross Martin-Wells

Department Chair

Amanda J. Reig

Project Description

Methyltransferases are a large class of enzymes that catalyze the transfer of methyl groups to various protein substrates. This reaction is observed in numerous cellular processes, including the regulation of gene expression through post-translational modifications of histone proteins. The overexpression of various methyltransferases has been implicated in multiple types of cancer, as well as cardiovascular and neurodegenerative diseases. The synthesis of selective, potent, and cell-active small molecule inhibitors of such enzymes would be useful in deducing their functions and is therefore an important area of research. This study aimed to produce numerous potential inhibitors that will be evaluated for their potency and selectivity towards different methyltransferases. In this work, various reaction conditions were tested for the deprotection of our simplest proposed inhibitor. Cation scavengers were employed to prevent side reactions that had been observed previously. Additionally, methods were developed for the use of analytical HPLC and preparative-LC in analyzing and purifying the crude reaction mixtures, respectively. Once a viable purification method is established, all compounds in our library will be deprotected, purified, and then tested for biological activity. Several iterations of the design and synthesis of compounds, followed by biological testing, will afford invaluable structure-activity relationship information.