McNair Scholar 2018 - Luis Ramirez
Luis Ramirez is a rising junior at the University of Minnesota - Twin Cities and is a Physiology major and Biochemistry minor. His research interests focus on the development of new drugs for disease intervention. He plans on attending graduate school for research in either Physiology or Medicinal Chemistry.
Quote from Luis Ramirez
My dream is to find new discoveries in medical advances to heal the sick while making it accessible to anyone. I also want to be a role model in the community to show and inspire that anyone can achieve their dreams.
Research project
Selective N-Terminal BET-Family Bromodomain Inhibitor Development by Targeting the ZA-Channel of Brd4
Abstract: Bromodomain containing proteins recognizing acetylated histone substrates are emerging clinical targets for cancer and other diseases. P38α kinase inhibitors were previously identified as selective N-terminal BET family bromodomain inhibitors. In our study molecule HU-10, a weak but selective inhibitor of Brd4-D1, served as a scaffold to design more potent inhibitors to increase bromodomain selectivity over p38α kinases. A crystal structure of HU-10 with BRD4-D1 reveals openings in Brd4 towards an area called the ZA channel. Analogs of HU-10 accessing this channel are designed and computationally screened with Maestro Schrodinger, testing for improvements in predicted docking scores. Docking scores of 1,4 and 1,5 triazole, amide, and thiazole containing analogues improved predicted binding affinities by two to four kilocalories/mol, 1,5 triazoles being most favored. A subset of molecules will be synthesized and evaluated for their binding properties with Brd4. Improved 1,5-triazole analogues could reduce off-target bromodomain binding toxicity and reduce kinase inhibition.
Faculty mentor
Dr. William C.K. Pomerantz is an Associate Professor of Chemistry and a McKnight Presidential Fellow at the University of Minnesota - Twin Cities. Dr. Pomerantz obtained his Chemistry B.S. degree from Ithaca College, New York in 2002 and his Ph.D. in Organic Chemistry from the University of Wisconsin - Madison in 2008. He is interested in chemical biology and synthesis of new molecules to understand interactions between disease-affiliated transcription factors. One approach his lab developed is the use of (_^19)F NMR. Dr. Pomerantz contributes through numerous publications about protein-protein interactions with a focus on epigenetics to study protein-ligand binding interactions.