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Eric Walters, PhD

Associate Dean of Research, Professor

D. Eric Walters, PhD, joined the College of Pharmacy Faculty Leadership Team in 2009 and was appointed Professor of Pharmaceutical Sciences in 2010. He is also Professor of Biochemistry and Molecular Biology in the Chicago Medical School. Dr. Walters received a BS in Pharmacy from the University of Wisconsin in 1974 and a PhD in Medicinal Chemistry in 1978. Following postdoctoral studies in the Chemistry Department at Indiana University, he carried out research in the food and pharmaceutical industries for 12 years. He joined the faculty of the Chicago Medical School in 1991. He has served as Principal Senator of the University Faculty Senate and as chair of the University Faculty Affairs Committee. In the Medical School, he was Course Director for the Molecular Cell Biology course for 10 years and taught in the Medical Biochemistry course. In the Graduate School, he developed and teaches two courses: Computer Applications in Biomedical Research, and The Art of Scientific Presentation. In the College of Pharmacy, he is Course Director for the Medicinal Chemistry course sequence. His research program is focused on computer modeling of proteins and computer aided drug design. He collaborates with Professor Arun Ghosh at Purdue University on the development of HIV protease inhibitors, and participated in the discovery of darunavir (Prezista®). He also collaborates with other investigators in the study of citrate transporters, potassium channels, and amino acid transporters. He has co-authored four books and over 90 scientific papers, holds two patents, and has given over 100 research presentations and invited lectures. Dr. Walters served as Secretary of the Medicinal Chemistry Division of the American Chemical Society for nine years (2011- 2019)

Courses

  • Medicinal Chemistry
  • Advanced Medicinal Chemistry I, II, III
  • Pharmaceutics I
  • Structure-Activity Relationships
  • Computer Applications in Biomedical Research
  • The Art of Scientific Presentation

Research

My research interest is in the application of computer modeling to drug design, protein structure-function relationships, and drug-receptor interactions. Molecular mechanics, molecular dynamics, and electronic structure calculations can provide insight into events at the molecular level which are not easily studied experimentally. Current problems of interest include:

  • Application of computer-adided drug design methodology to the discovery of new anti-viral drugs. A particular interest is inhibition of the HIV protease enzyme, in collaboration with Professor Arun Ghosh, Purdue University.
  • Mechanisms of sweet and bitter taste transduction. Interactions between sweet and bitter taste. Inhibition of bitter taste.
  • Modeling a potassium channel, in collaboration with Professor Henry Sackin.
  • Modeling a mitochondrial citrate transport protein, in collaboration with Professor Ron Kaplan. 

Recent Publications

  1. Orexin Antagonists: A Wake-up Call for Medicinal Chemists? D.E. Walters. J. Med. Chem., 63(4):1526-1527, 2020. PMID: 32073265
  2. Potent HIV-1 protease inhibitors incorporating squaramide-derived P2 ligands: Design, synthesis, and biological evaluation. A.K. Ghosh, J.N. Williams, S Kovela, J. Takayama, H.M. Simpson, D.E. Walters, S.I. Hattori, M. Aoki, and H. Mitsuya. Med. Chem. Lett., 29(18):2565-2570, 2019. PMID: 31416666
  3. Variation of the aryl substituent on the piperazine ring within the 4-(piperazin1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases. C.R. Kent, M. Bryja, H.A. Gustafson, M.Y. Kawarski, G. Lenti, E.N. Pierce, R.C. Knopp, V. Ceja, B. Pati, D.E. Walters, and C.E. Karver. Bioorg. Med. Chem. Lett., 26(12):5476-5480, 2016. PMID: 27777011
  4. Variation of the aryl substituent on the piperazine ring within the 4-(piperazin1-yl)-2,6-di(pyrrolidin-1-yl)pyrimidine scaffold unveils potent, non-competitive inhibitors of the inflammatory caspases. C.R. Kent, M. Bryja, H.A. Gustafson, M.Y. Kawarski, G. Lenti, E.N. Pierce, R.C. Knopp, V. Ceja, B. Pati, D.E. Walters, and C.E. Karver. Bioorg. Med. Chem. Lett., Epub ahead of print, Oct 12, 2016. PMID: 27777011.
  5. Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives. O.A. Phillips, R. D'Silva, T.O. Bahta, L.H. Sharaf, E.E. Udo, L. Benov, and D.E. Walters. Eur. J. Med. Chem., 106:120-131, 2015. PMID: 26536532
  6. Antipsychotics inhibit glucose transport: determination of olanzapine binding site in Staphylococcus epidermidis glucose/H+ symporter. P. Babkin, A.M. George Thompson, D.E. Walters, and J.-Y. Choe. FEBS Open Bio, 5:335- 340, 2015. PMID: 25941630.
  7. Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1-P2 ligands. A.K. Ghosh, G.E. Schilz, L.N. Rusere, H.L. Osswald, D.E. Walters, M. Amano, and H. Mitsuya. Org. & Biomol. Chem., 12:6842-6854, 2014. PMID: 25050776.
  8. Can Diet Soft Drinks Make You Fat? D.E. Walters. Medscape, http://www.medscape.com/viewarticle/810738, 2013.
  9. Team-Based Learning Applied to a Medicinal Chemistry Course. D.E. Walters. Med. Principles & Practice, 22:2-3, 2013. PMID: 23006824.
  10. Properties of two cataract associated mutations located in the N-terminus of Connexin 46. J.-J. Tong, B.C.H. Sohn, A. Lam, D.E. Walters, B.M. Vertel, and L. Ebihara. Amer. J. Physiol: Cell Physiol., 304:C823-C832, 2013. PMID: 23302783.
  11. Oligomycin frames a common drug-binding site in the ATP synthase. J. Symersky, D. Osowski, D.E. Walters, and D.M. Mueller. Proc. Natl. Acad. Sci. USA, 109:13961-13965 (2012). PMID: 22869738
  12. Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P2 Ligands: Structure-Activity Studies and Biological Evaluation. A.K. Ghosh, B.D. Chapsal, A. Baldridge, M.P. Steffey, D.E. Walters, Y. Koh, M. Amano, and H. Mitsuya. J. Med. Chem., 54:622-634 (2011). PMID: 21194227.
  13. Binding of Glutamate to the Umami Receptor. J.J. López Cascales, S.D. Oliveira Costa, B.L. de Groot, and D.E. Walters. Biophys. Chem., 152:139- 144, 2010. PMID: 20961679
  14. Conformational changes in BAK, a pore-forming proapoptotic Bcl-2 family member, upon membrane insertion and direct evidence for the existence of BH3:BH3 contact interface in BAK homooligomers. K.J. Oh, P. Singh, K. Lee, K. Foss, S. Lee, M. Park, S. Lee, S. Aluvila, M. Park, P. Singh, R.-S. Kim, J. Symersky, and D.E. Walters. J. Biol. Chem., 285:28924-28937, 2010. PMCID: PMC2937919
  15. The yeast mitochondrial citrate transport protein: molecular determinants of its substrate specificity. S. Aluvila, R. Kotaria, J. Sun, J.A. Mayor, D.E. Walters, D.H.T. Harrison, and R.S. Kaplan. J. Biol. Chem., 285:27314-27326, 2010. PMCID: PMC2930730
  16. Mitochondrial and plasma membrane citrate transporters: discovery of selective inhibitors and application to structure/function analysis. J. Sun, S. Aluvila, R. Kotaria, J.A. Mayor, D.E. Walters, and R.S. Kaplan. Molec. Cell. Pharmacol., 2:101-110, 2010. PMCID: PMC2913483
  17. A conserved arginine near the filter of Kir1.1 controls Rb/K selectivity. H. Sackin, M. Nanazashvili, H. Li, L.G. Palmer, and D.E. Walters. Channels, 4:203-214, 2010.
  18. Probing the Effect of Transport Inhibitors on the Conformation of the Mitochondrial Citrate Transport Protein via a Site-Directed Spin Labeling Approach. J.A. Mayor, J. Sun, R. Kotaria, D.E. Walters, K.-J. Oh, and R.S. Kaplan. J. Bioenerg. Biomembr., 42:99-109. 2010. PMCID: PMC2867622
  19. Synthesis and biological evaluation of novel allophenylnorstatine-based HIV1 protease inhibitors incorporating high affinity P2-ligands. A.K. Ghosh, S. Gemma, E. Simoni, A. Baldridge, D.E. Walters, K. Ide, Y. Tojo, Y. Koh, M. Amano, and H. Mitsuya. Bioorg. Med. Chem. Lett., 20, 1241-1246. 2010.
  20. Ion Selectivity of α-Hemolysin with β-Cyclodextrin Adapter: II. Multi-Ion Effects Studied with Grand Canonical Monte Carlo/Brownian Dynamics Simulations. B. Egwolf, Y. Luo, D.E. Walters, and B. Roux. J. Phys. Chem. B, 114, 2901-2909. 2010. PMCID: PMC2843906
  21. Ion Selectivity of α-Hemolysin with β-Cyclodextrin Adapter: I. Single Ion Potential of Mean Force and Diffusion Coefficient. Y. Luo, B. Egwolf, D.E. Walters, and B. Roux. J. Phys. Chem. B, 114, 952-958. 2010. PMCID: PMC2847479
  22. Inhibitors of the Mitochondrial Citrate Transport Protein: Validation of the Role of Substrate Binding Residues and Discovery of the First Purely Competitive Inhibitor. S. Aluvila, J. Sun, D.H.T. Harrison, D.E. Walters, and R.S. Kaplan. Mol. Pharmacol. 77, 26-34. 2010. PMCID: PMC2802432