McNair Scholar 2023 Baraa Al-Jasim
Baraa Al-Jasim is a Junior at the University of Minnesota studying chemistry and Japanese. Her research interests include the design and synthesis of organic compounds with potential therapeutic properties. Baraa plans to pursue higher education and earn a Ph.D. in chemistry to become a researcher and professor.
My dream is to become a professor and researcher to empower students like myself to reach their full potential and engage them to push the boundaries of scientific advancements
Research project
Synthesis and Structure-Activity-Relationship Study of 1,4-Acylthiazepanes as BD2-Selective BET Bromodomain Inhibitors
Abstract: Selective inhibition of the bromodomain and extra-terminal domain (BET) family of proteins is a promising method to regulate gene expression and disrupt disease-associated pathways. Current Inhibitors that target the D2 bromodomain attenuate undesirable side effects in clinical settings, minimizing their therapeutic potential. Recently, the Pomerantz lab developed inhibitors based on the 1,4-acylthiazepane scaffold identified from a small molecule screen of 3D-enriched fragments, which subsequently were shown to target the D2 bromodomain of BET proteins. 1,4-acylthiazepanes’ high 3D character allows for favorable interactions with the D2 bromodomain as it mimics the acetylated lysine on the histone tail and may potentially engage a non-conserved histidine. In this study, we synthesized 1,4-acylthiazepanes, with varying substituents on the benzene ring which can interact with histidine. Competitive Alpha Screen assays were employed to evaluate the selectivity and binding affinity for D2 bromodomains. By varying substituents on the benzene ring, we can explore the electronic properties to further optimize selectivity and affinity to target D2 bromodomains.
Faculty mentor
William Pomerantz is the Merck Professor Chemistry at the University of Minnesota. Prof. Pomerantz received his B.S. in chemistry from Ithaca College in 2002, followed by a Fulbright Fellowship at ETH, Zürich He obtained a Ph.D. in chemistry at the University of Wisconsin-Madison and was a postdoctoral fellow under Prof. Anna Mapp at the University of Michigan. He joined the chemistry faculty at the University of Minnesota in 2012. His research focuses on the development of chemical biology and medicinal chemistry approaches for modulating protein-protein interactions involved in transcriptional complexes, most notably those involved in promoting cancer and inflammatory disease.