[Research Interests] [Representative Publications] [Lab Members] RESEARCH INTERESTSThe ultimate goal of biomedical research is to cure disease. Fundamental research in this laboratory has resulted in the development of a thermodynamic platform for drug discovery and optimization. This platform is permanently improved and simultaneously applied to the discovery and optimization of novel drugs against important diseases for which no successful therapies are available. HIV/-1 Protease Inhibitors. HIV/AIDS Plasmepsin inhibitors. Malaria HCV Protease inhibitors. Hepatitiis C. Coronavirus 3CL-pro Protease Inhibitors. SARS and other viral infections. HIV-1 gp120 inhibitors. HIV/AIDS HIV-1 Nef inhibitors. HIV/AIDS REPRESENTATIVE PUBLICATIONS 2007 - 2009• S. Muzammil, A. A. Armstrong, L. W. Kang, A. Jakalian, P. R Bonneau, V. Schmelmer, L. M. Amzel and E. Freire (2007) Unique Thermodynamic Response of Tipranavir to HIV-1 Protease Drug Resistance Mutations J. Virology, 81, 5144-5154 • Koushi Hidaka, Tooru Kimura, Yumi Tsuchiya, Mami Kamiya, Adam J. Ruben, Ernesto Freire, Yoshio Hayashi and Yoshiaki Kiso (2007) Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II. Bioorg. Medicinal Chem. Letters 17, 3048-3052 • Lafont, V., Armstrong, A.A., Ohtaka, H., Kiso, Y., Amzel, M. and Freire, E. (2007) Compensating Enthalpic and Entropic Changes Hinder Binding Affinity Optimization. Chem. Biol. Drug. Design 69, 413-422 • Freire, E. A new era for microcalorimetry in drug development (2007) European Pharmaceutical Review 5, 73-78 • Schon, A. and Freire, E. Strategies for targeting HIV-1 envelope glycoprotein gp120 in the development of new antivirals (2007) Future Medicine 1, 223-229 • Bower, E., Bacha, U.M., Kawasaki, Y. and Freire, E. Inhibition of HIV-2 Protease by HIV-1 Protease Inhibitors in Clinical Use (2008) Chem. Biol. Drug. Design 71 298-305 • Cremades, N., Velazquez-Campoy, A., Freire, E. and Sancho, J. The Flavodoxin from Helicobacter pylori: Structural Determinants of Thermostability and FMN Cofactor Binding (2008) Biochemistry 47 627-639 • Hosahudya Gopi, M.Umashankara, Vanessa Pirrone, Judith LaLonde, Navid Madani, Ferit Tuzer, Sabine Baxter, Isaac Zentne, Simon Cocklin, Navneet Jawanda, Shendra R. Miller, Arne Schön, Jeffrey C. Klein, Ernesto Freire, Fred C. Krebs, Amos B. Smith III, Joseph Sodroski and Irwin Chaiken (2008) Structural Determinants for Affinity Enhancement of a Dual Antagonist Peptide Entry Inhibitor of Human Immunodeficiency Virus Type-1 J. Medicinal Chem. 51 2638-2647 • Bacha, U., Barrila, J., Gabelli, S.B., Kiso, Y. Amzel, L.M. Freire, E. (2008) Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CLpro Chem. Biol. Drug. Design 72, 34-49 • Freire, E. A new era for microcalorimetry in drug development (2008) American Pharmaceutical Review 11, 118-123 • Freire, E. (2008) Do Enthalpy and Entropy Distinguish First in Class From Best in Class? Drug Discovery Today 13, 869-874 • Freire, E., Schön, A., Velazquez-Campoy, A. (2009) Isothermal Titration Calorimetry: General Formalism Using Binding Polynomials. Methods in Enzymology. 455, 127- 155 • Navid Madani, Arne Schon, Amy M. Princiotto, Judith M. LaLonde, Joel R. Courter, Takahiro Soeta, Danny Ng, Liping Wang, Evan T. Brower, Shi-Hua Xiang, Young Do Kwon, Chih-chin Huang, Richard Wyatt, Peter D. Kwong, Ernesto Freire, Amos B. Smith III and Joseph Sodroski (2008) Small-Molecule CD4 Mimics Interact with a Highly Conserved Pocket on HIV-1 gp120. Structure 11, 1689-1701 • Hidaka, K., Kimura, T., Ruben, A. J., Uemura, T., Kamiya, M., Kiso, A., Okamoto, T., Tsuchiya, Y., Hayashi, Y., Freire, E. and Kiso, Y. (2008) Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin. Bioorganic and Medicinal Chemistry, 16 10049-10060 • Freire, E. A Thermodynamic Platform for Drug Discovery and Optimization (2008) in Towards Drugs of the Future, pages 13-22 Kruse, C.G. and Timmerman, H. Eds. • Freire, E. ITC: Affinity is not everything (2009) European Pharmaceutical Review 14, 44-47 • Brower, E. T., Schon, A., Klein, J. C., and Freire, E. Binding Thermodynamics of the N-Terminal Peptide of the CCR5 Coreceptor to HIV-1 Envelope Glycoprotein gp120 (2009) Biochemistry 48, 779-785 • Chunlong Ma, Alexei Polishchuk, Yuki Ohigashi, Amanda Stouffer, Arne Schön, Emma Magavern, James D. Lear, Ernesto Freire, Robert A. Lamb, William F. DeGrado, and Lawrence H. Pinto Identification of the Functional Core of the Influenza A Virus A/M2 Proton-Selective Ion Channel (2009) Proceedings of the National Academy of Sciences 106:12283-12288 • Regnier Thomas, Diganta Sarma,Koushi Hidaka, Usman Bacha, Ernesto Freire, Yoshio Hayashi and Yoshiaki Kiso, New Developments for the Design, Synthesis and Biological Evaluation of Potent SARS-CoV 3CLpro Inhibitors (2009) Bioorganic & Medicinal Chemistry Letters 19, 2722-2727 • Ernesto Freire A thermodynamic approach to the optimization of drug candidates (2009) Chem Biol Drug Design In Press Lab MembersResearch Scientist: Postdoctoral Fellows: Graduate Student: |
