The North Jersey ACS NMR Topical Group is pleased to presents its April meeting at Princeton, Wednesday, April 11, 2018 [ register ]
Alan Gibbs, PhD
Principal Scientist at Janssen Pharmaceuticals
“Inhibitor Bound Dengue NS2B-NS3pro Reveals Multiple Dynamic Binding Modes”
Dengue virus poses a significant global health threat as the source of increasingly deleterious dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. As no specific antiviral treatment exists for dengue infection, considerable effort is being applied to discover therapies and drugs for maintenance and prevention of these afflictions. The viral genome encodes the enzyme to carry out cleavage of the large polyprotein, specifically the NS2B-NS3pro cofactor-protease complex—a target of high interest for drug design. One class of recently discovered NS2B-NS3pro inhibitors is the substrate-based trifluoromethyl ketone containing peptides. These compounds interact covalently with the active site Ser135 via a hemiketal adduct. A detailed picture of the intermolecular protease/inhibitor interactions of the hemiketal adduct is crucial for rational drug design. We show, through the use of protein- and ligand-detected solution-state 19F and 1H NMR methods, an unanticipated multibinding mode behavior of a representative of this class of inhibitors to dengue NS2B-NS3pro. Our results illustrate the highly dynamic nature of both the covalently bound ligand and protease protein structure, and the need to consider these dynamics when designing future inhibitors in this class.
6:00 pm Dinner (in Frick Atrium)
7:00 pm Seminar (in Seminar Room A81)
$5 for everyone. No charge for seminar only.
Frick Chemistry Laboratory
Princeton, NJ 08544 [ directions ]
Parking: Parking will be available in Lot 21 (see map link given above under Directions)
Public Transit: It is possible to take NJ Transit all the way to Princeton campus (the symposium location is ~ 10 min walk from the train station). Take the Northeast Corridor NJ transit train to Princeton Junction, then transfer to the small “dinky” train that ends on campus (5 min train ride).
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