Sequoia Sciences & Protasis Announce Research Partnership Agreement
MicroFlow NMR Speeds Confirmation and Dereplication in Natural Products Discovery

Marlboro, Mass., May 2, 2002 -- Sequoia Sciences, Inc., a drug discovery company, and Protasis/MRM Corporation, an integrator of micro-analytical systems to the life science industries, announced today they have formed a research partnership that calls for Sequoia Sciences to deploy and validate Protasis/MRM’s patented, microflow NMR probes and new, microfluidic sample management devices. The three companies’ integrated technology platforms of rapid parallel purification systems with multiple detection methods, including state-of-the-art multi-channel MS analysis and NMR probes, along with microfluidics sample pathways will allow each company to greatly accelerate its productivity.

Sequoia aids high-throughput screening (HTS) programs by providing novel libraries of chemically diverse compounds that it isolates from plants, while Protasis, a spin-off of Waters Corporation, is leveraging its expertise in HPLC and microfluidics to develop leading-edge molecular analysis and life science automation tools for research and application scientists. Magnetic Resonance Microsensors (MRM), an operating unit of Protasis, is the pioneer of capillary-scale, microflow NMR probes using miniaturized detector flowcells. MRM’s new-to-market, proton-only and carbon indirect gradient CapNMRTM flowprobes and the just introduced, Protasis HTSL-1100 sample loader form the basis of the technological research agreement among the three companies.

The unprecedented mass sensitivity of the microflow NMR probe coupled with the high-throughput, microfluidic sample manager developed expressly for use with the flowprobes, now allows Sequoia to acquire 1D proton and 2D Gradient COSY NMR spectra on quantities of less than 10 micrograms in under ten minutes in its pursuit of rapid structure elucidation. Sequoia was among the first companies to validate the MRM microflow probe when introduced last year and was the first to use the just introduced indirect Proton/Carbon Gradient probe. With the aid of this probe, they have been able to identify greater than twenty new molecular entities (NME’s) within the past six months, a remarkable achievement in drug discovery productivity. The two prongs of Sequoia’s successful strategy are: (1) purification optimized by multi-stage separations methods and (2) structure elucidation using micro-scale NMR. This strategy dovetails with Protasis’ mission as a discovery tools provider.

The first of these strategic tools is available today as a standard Protasis/MRM product, the groundbreaking CapNMR Probe. In recent years, impressive gains in NMR sensitivity from increased magnet field strengths have pushed NMR probe development to keep pace, resulting in the introduction of new and technically challenging probe technologies. The cryo-cooled coil designs and now the CapNMR microcoil probe are two of the leading technologies that have recently been introduced. With microcoils, this gain in sensitivity comes from a dramatic reduction in flowcell volume, spurring NMR data acquisitions on mass-limited samples. With the CapNMR probe’s miniature coil size and higher filling factors, less solvent loading has resulted in fewer non-deuterated artifacts and less sample degradation. For Sequoia’s natural product compounds, this reduction by several orders of magnitude of the solvent-to-sample ratio has been an extraordinary benefit.

"The generation of tubeless NMR is now upon us," says Mark O'Neil-Johnson, Director of Research Partnerships of Sequoia Sciences and former West Coast Applications Manager of Bruker Instruments, Inc. "And now, the convenience of sample loading with the HTSL-1100 linked to the CapNMR probe has allowed us to rapidly acquire NMR data in a fraction of the time required by conventional probe technology. Also, the tremendous reduction in necessary solvent, compared to other advanced probe technologies, has allowed Sequoia to acquire proton data in order to quickly de-replicate our sample library, alleviating the need to recollect or refractionate biomass."

Going forward, Protasis will support the second leg of Sequoia’s strategy by providing additional separations technology to help manage Sequoia’s drug leads, including its patented Dynamic Focusing technique, that allows ultra-high resolution purification of selected target molecules from complex mixtures. This electrofocusing technique can also concentrate target molecules to high levels prior to automatically loading samples into the microflow NMR probe. The combination of higher concentrations to boost signal-to-noise ratio and lower flowcell volumes to reduce spectral acquisition times gives discovery researchers the power of simultaneous sensitivity and speed.

David Strand, CEO of Protasis Corporation, believes that Sequoia has identified a major new trend in analytical instrumentation. "Miniaturization lowers dispersion in separation columns and improves resolution. Microvolume flowcells similarly reduce background noise and shorten signal acquisition times in detectors. The combination of multiple microcomponents arranged into fluidic integrated circuit arrays (FICµS™) is enabling the design of new instrument functions that will extend analytical performance well beyond current norms to provide custom molecular microprocessing. High-resolution, multi-dimensional purification and information-rich, structure-based screening, the two elements in Sequoia's successful strategy, will improve drug discovery productivity geometrically. These new tools arrive just as the proteomics revolution is presenting an expanding molecular universe of new protein targets and new drug leads to create a combinatorial jigsaw puzzle of galactic proportions."

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CapNMR™ = capillary microflow NMR probe
Ficμs™ = fluidic integrated circuit for microseparations

For more information, contact:
Mark O'Neil Johnson
Director of Research Partnerships
Sequoia Sciences
11199 Sorrento Valley Road
San Diego, CA 92121
Tel: 858-623-0800, ext. 104

Joyce King
Marketing Communications
Protasis Corporation
734 Forest Street
Marlboro, MA 01752
Tel: 508-481-4163
www.protasis.com