Dr. Freire’s research focuses on structure-based thermodynamics of molecular recognition and function.
The fundamental research conducted in Dr. Freire’s laboratory has led to the development of a thermodynamic platform for drug discovery and optimization. The platform is used both to discover and to optimize novel drugs so that they can be used to treat a variety of diseases. The optimization platform is designed to achieve very high binding affinity and selectivity as well as appropriate pharmacokinetics. Dr. Freire’s team is currently investigating drug targets that include: HIV/-1 protease inhibitors (HIV/AIDS), plasmepsin inhibitors (malaria), HCV protease inhibitors (hepatitis C), coronavirus 3CL-pro protease inhibitors (SARS and other viral infections), HIV-1 gp120 inhibitors (HIV/AIDS), chymase inhibitors (cardiovascular disease) and beta lactamase inhibitors (antibiotic resistance).
Melillo B, Liang S, Park J, Schön A, Courter JR, LaLonde JM, Wendler DJ, Princiotto AM, Seaman MS, Freire E, Sodroski J, Madani N, Hendrickson WA, Smith AB 3rd. "Small-molecule CD4-mimics: Structure-based optimization of HIV-1 entry inhibition." ACS Med Chem Lett. 2016 Jan 19;7(3):330-4. doi: 10.1021/acsmedchemlett.5b00471. eCollection 2016 Mar 10.
Schön A, Freire E. "Three easy pieces." Biochim Biophys Acta. 2016 May;1860(5):975-80. doi: 10.1016/j.bbagen.2015.12.003. Epub 2015 Dec 9.
Clarkson BR, Schön A, Freire E. "Conformational stability and self-association equilibrium in biologics." Drug Discov Today. 2016 Feb;21(2):342-7. doi: 10.1016/j.drudis.2015.11.007. Epub 2015 Nov 19. Review.
Chauhan J, Chen SE, Fenstermacher KJ, Naser-Tavakolian A, Reingewertz T, Salmo R, Lee C, Williams E, Raje M, Sundberg E, DeStefano JJ, Freire E, Fletcher S. "Synthetic, structural mimetics of the β-hairpin flap of HIV-1 protease inhibit enzyme function." Bioorg Med Chem. 2015 Nov 1;23(21):7095-109. doi: 10.1016/j.bmc.2015.09.002. Epub 2015 Sep 7.
Xu Q, Ensign LM, Boylan NJ, Schön A, Gong X, Yang JC, Lamb NW, Cai S, Yu T, Freire E, Hanes J. "Impact of surface polyethylene glycol (PEG) density on biodegradable nanoparticle transport in mucus ex vivo and distribution in vivo." ACS Nano. 2015 Sep 22;9(9):9217-27. doi: 10.1021/acsnano.5b03876. Epub 2015 Aug 31.