Bringing Back Nature to a Drug Discovery Program

Bringing Back Nature to a Drug Discovery Program

Mark O'Neil-Johnson, Russell Williams, Courtney Starks and Gary Eldridge

Sequoia Sciences Inc., Saint Louis, Missouri, USA

Natural product chemistry has traditionally been a long and time-consuming process for drug discovery research. From extraction, Isolation and purification to structure elucidation, active fraction identification down to the compound level is a real challenge in creating value for today's high thru-put screening (HTS) programs.

Sequoia Sciences has developed rugged HPLC extraction and isolation methodologies for purified natural product chromatographic fractions that fit right into HTS screening platforms. Sequoia has also overcome the barrier of structure elucidation on minute quantities, i.e. microgram quantities of active natural product compounds, a necessary requirement in satisfying the "H" criteria in high-throughput screening programs. A successful natural product discovery program in today's drug discovery process must have all of these elements of the isolation process rapidly completed and validated as well as rapid structure elucidation to follow up on active leads. This must be done on scales approaching traditional screening quantities.

With the introduction of the CapNMRR and MicroCryoProbe technologies, new opportunities were created to take the sample requirements down to the microgram scale. From complete NMR data set acquisitions on compounds from HPLC isolations at the single digit microgram scale, Sequoia has been able to accelerate the discovery of active and novel compounds from natural product sources.

Sequoia's extraction and purification scheme utilizing advanced analytical technology to create a robust pipeline of natural product samples normalized for HTS protocols have resulted in two preclinical programs in bacterial biofilms and cancer. These results will be presented. Sequoia has enabled a way for biology and chemistry to uncover biologically active unknown structures at a fraction of the time without the need to recollect and scale up. By eliminating this process and utilizing modern Instrumentation, natural product research can realize its full potential in drug discovery.