Graduate Students Choice Lecture
GRADUATE STUDENTS CHOICE LECTURE 2010
Title: Harnessing the power of organic synthesis to address the challenges of today's medicine
Presented by: Dr. Arun K. Ghosh
Ian P. Rothwell
Distinguished Professor Organic
Chemistry/Medicinal Chemistry Purdue
University, West
Lafayette, IN Download the flyer here.
Date: May 21, 2010
Time: 12:30 pm
Location: College of Pharmacy Room B36
Abstract
Our interest in the chemistry and
biology of natural products brought a unique perspective to our work in the
area of biomedical research involving the power of organic synthesis. It all
started as a seemingly academic pursuit in which we intended to design
bioactive natural product-derived scaffolds or ligands to mimic the biological
mode of action of peptide bonds. This would provide a means to alleviate some
of the inherent problems associated with peptide-based drugs. The significant
challenges presented by the stereochemical complexity of such design and the
necessary multi-step synthesis portrayed the strategy as a purely academic
endeavor. Our in-depth work in the design of therapeutically relevant enzyme
inhibitors began to demonstrate the significance of this strategy.Aspartic acid proteases are involved in the pathogenesis of many of human diseases and not surprisingly, aspartyl proteases have become important targets for drug-design and development. The introduction of HIV protease inhibitors in highly active antiretroviral therapy (HAART) continues to be the major treatment regimen for HIV/AIDS. However, one of the major challenges of HAART-therapy is the emergence of multidrug-resistant HIV-1 variants. In this context, our research efforts targeting the protein backbone led to structurally diverse new classes of potent HIV-1 protease inhibitors with impressive resistance profiles. Darunavir, designed based upon our ‘backbone binding concept’ has been recently approved for the treatment of experienced HIV/AIDS patients harboring multidrug-resistant HIV. Another aspartyl protease, memapsin 2 (β-secretase, BACE-1), has also become an important drug-design target for the treatment of Alzheimer’s disease. Our structure-based design has led to the development of a number of potent and selective inhibitors of memapsin 2 for clinical development. This presentation will feature novel design-concepts, general strategies and development tools for HIV-1 protease inhibitors against HIV/AIDS and β-secretase inhibitors against Alzheimer’s disease.
Previous seminars
2009"Taxol, Tubulin, and Tumors: Challenges in New Era of Cancer Therapeutics"
Susan Band Horwitz, PhD. Distinguished Professor, Department of Molecular Pharmacology at Albert Einstein College of Medicine, Rose C. Falkenstein Professor of Cancer Research.
2008
"Discovery of Nitric Oxide and Cyclic GMP Signaling and Their Role in Drug Discovery and Development"
Ferid Murad, MD, PhD. Nobel Prize in Physiology or Medicine 1998, The University of Texas, Health Science Center at Houston
2007
"Venomous Fish-Hunting Cone Snails: Drug Development from Animal Biodiversity"
Baldomera Olivera, PhD. Distinguished Professor of Biology, University of Utah
2006
David Graham, MD, MPH. FDA Medical Officer