Chemistry & Biochemistry
November 7, 2012
Jeremy Wulff, Ph.D.
CRC (Canada Research Chair – Bioactive Small Molecule Synthesis)
Department of Chemistry
University of Victoria
Wherefore Rigidity? Building the Case for Structural Complexity in Neuraminidase Inhibitors
Tuesday, Nov. 13, 2012
12:15 – 1:30 pm
C640 - UHall
All are welcome to attend
Rapid mutation of the influenza virus through genetic mixing raises the prospect of new strains that are both highly transmissible and highly lethal, and which have the capability to evade both immunization strategies (via mutation of hemagglutinin) and current therapies (via mutation of neuraminidase).
The ability of influenza to adapt to existing therapeutics points to a need for the creation of novel drug scaffolds that can be used for next-generation neuraminidase inhibitors. Moreover, many recent reports suggest that selective inhibition of human neuraminidases could lead to novel treatments for several types of cancer.
Here we report a synthetic strategy for a new class of rigid, bicyclic inhibitor scaffolds with application to the development of novel neuraminidase inhibitors. Small-molecule X-ray studies and enzyme-inhibition data confirm that our newly designed scaffolds have the required structural properties to pre-position pendant functional groups into the correct orientations for binding the enzyme active site.