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Andrew D Mesecar


  • Head BCHM/Professor BCHM & BioSci/PCCR Deputy Director
BCHM Room 121A

Area of Expertise: Gene-to Lead Drug Discovery

The fundamental research interests of the Mesecar lab involve elucidating the molecular mechanisms and function of therapeutic enzymes and proteins.  We wish to understand at the molecular level how enzymes and proteins recognize their substrates, catalyze their requisite chemical reactions, and trigger signal-transduction cascades. Our ultimate goal is to utilize this fundamental scientific knowledge to develop new therapeutics to treat cancer and infectious diseases. 

To achieve these goals, we integrate a variety of state-of-the-art research tools and approaches including X-ray crystallography, enzyme chemistry and kinetics, molecular biology, bioinformatics, mass spectrometry, and computational chemistry to gain an understanding of the role of protein dynamics and conformational change in molecular recognition and catalysis. We then couple these technologies with high-throughput screening and structure-based design to develop compounds capable of modulating the activity of enzymes and receptors involved in cancer chemoprevention, cancer cell proliferation, cell longevity, and bacterial and viral pathogenesis.

Selected Publications

Ghosh, A. K., Brindisi, M., Yen, Y. C., Lendy, E. K., Kovela, S., Cárdenas, E. L., . . . Mesecar, A. D. (2019). Highly Selective and Potent Human β-Secretase 2 (BACE2) Inhibitors against Type 2 Diabetes: Design, Synthesis, X-ray Structure and Structure-Activity Relationship Studies. ChemMedChem. doi:10.1002/cmdc.201800725

Ghosh, A. K., Ghosh, K., Brindisi, M., Lendy, E. K., Yen, Y. C., Kumaragurubaran, N., . . . Mesecar, A. D. (2018). Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand. Bioorganic & medicinal chemistry letters, 28(15), 2605-2610. doi:10.1016/j.bmcl.2018.06.045

Ghosh, A. K., Brindisi, M., Yen, Y. C., Cárdenas, E. L., Ella-Menye, J. R., Kumaragurubaran, N., . . . Mesecar, A. D. (2017). Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1'-P2' ligands. Bioorganic & medicinal chemistry letters, 27(11), 2432-2438. doi:10.1016/j.bmcl.2017.04.011

Ghosh, A. K., Reddy, B. S., Yen, Y. C., Cardenas, E., Rao, K. V., Downs, D., . . . Mesecar, A. D. (2016). Design of Potent and Highly Selective Inhibitors for Human β-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes. Chemical science, 7, 3117-3122. doi:10.1039/C5SC03718B

Jain, A. D., Potteti, H., Richardson, B. G., Kingsley, L., Luciano, J. P., Ryuzoji, A. F., . . . Moore, T. (2015). Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators. European journal of medicinal chemistry, 103, 252-68. doi:10.1016/j.ejmech.2015.08.049

Ghosh, A. K., Brindisi, M., Yen, Y. C., Xu, X., Huang, X., Devasamudram, T., . . . Tang, J. (2015). Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand. Bioorganic & medicinal chemistry letters, 25(3), 668-72. doi:10.1016/j.bmcl.2014.11.087

Vickman, R. E., Crist, S. A., Kerian, K., Eberlin, L., Cooks, R. G., Burcham, G. N., . . . Ratliff, T. L. (2016). Cholesterol Sulfonation Enzyme, SULT2B1b, Modulates AR and Cell Growth Properties in Prostate Cancer. Molecular cancer research : MCR, 14(9), 776-86. doi:10.1158/1541-7786.MCR-16-0137

Zhai, X., Go, M. K., O'Donoghue, A. C., Amyes, T. L., Pegan, S. D., Wang, Y., . . . Richard, J. P. (2014). Enzyme architecture: the effect of replacement and deletion mutations of loop 6 on catalysis by triosephosphate isomerase. Biochemistry, 53(21), 3486-501. doi:10.1021/bi500458t

Abuhammad, A., Al-Aqtash, R. A., Anson, B. J., Mesecar, A. D., & Taha, M. O. (2017). Computational modeling of the bat HKU4 coronavirus 3CL<sup>pro</sup> inhibitors as a tool for the development of antivirals against the emerging Middle East respiratory syndrome (MERS) coronavirus. Journal of molecular recognition : JMR, 30(11). doi:10.1002/jmr.2644

Daczkowski, C. M., Dzimianski, J. V., Clasman, J. R., Goodwin, O., Mesecar, A. D., & Pegan, S. D. (2017). Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species. Journal of molecular biology, 429(11), 1661-1683. doi:10.1016/j.jmb.2017.04.011

Awards & Honors

(1999) American Association of Colleges of Pharmacy New Investigator Award. American Association of Colleges of Pharmacy.

(1984) U. S. Air Force ROTC Four-Year Scholarship. U. S. Air Force ROTC.

Department of Biochemistry, 175 South University Street, West Lafayette, IN 47907-2063 USA, (765) 494-1600

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