Mark O'Neil-Johnson, Sequoia Sciences, Saint Louis, MO

Title:  Bringing Nature Back to Drug Discovery                           (View full .pdf abstract)

Sequoia Sciences was founded to deliver to the drug discovery process a structurally diverse library of natural products isolated from plants.  The proprietary design of this library allows the screening of these compounds at optimal HTS concentrations without non-drug-like interferences.  In order to facilitate the rapid identification of potential leads, Sequoia has built an analytical process that can facilitate the rapid isolation and structure elucidation of active compounds.  Paramount to the success of our structure elucidation efforts, Sequoia has relied solely on NMR data acquisition using the Protasis’ remarkable CapNMR™ probe.  Moreover, we have applied our proprietary chemistry procedures and innovative technologies in our internal antibacterial program, discovering a variety of compounds that show promising inhibition of bacterial biofilms and are synthetically accessible.

In an NIH funded collaboration with Montana State University’s Center for Biofilm Engineering, Sequoia has discovered new inhibitors of bacterial biofilms.  During research under this collaboration, novel compounds have been identified that demonstrate biofilm inhibition in Pseudomonas aeruginosa (PA01) and multiple strains of Escherichia coli, including uropathogenic clinical strains isolated from patients with urinary tract infections.  Through collaborations at Washington University School of Medicine and the University of Connecticut, this biofilm research was expanded to include multiple species of bacteria and micro array data.

This talk will discuss a specific example of a set of compounds that were discovered from our natural product collection that exhibits remarkable activity against uropathogenic clinical strains of E. coli.  Detailed will be the scientific strategy that Sequoia employs in order to uncover the chemical diversity in natural products that has gone untapped in plants.  Expanding upon known advanced analytical technology, the techniques that Sequoia has employed to accelerate the drug discovery process from a natural product source will be explained in detail.  Overcoming the challenges in working with natural products, both the failures and successes will also be shared.  It will be obvious to the audience how Sequoia has been able to generate a robust supply of natural product compounds to drive this research project.