SEQUOIA SCIENCES

Establishing mutually beneficial relationships between countries with rich biological diversity and chemical discovery programs has become increasingly complex. If properly negotiated, countries possessing rich biological diversity could benefit from sources of sustained income and technology transfer, and chemical discovery programs could continue to discover diverse, novel molecules with selective biological activity.

Sequoia Sciences [website] and the Missouri Botanical Garden have formed a unique, interdisciplinary team to provide a complete solution ranging from access for plant collection to the distribution of dereplicated compounds. The results are equitable and sustainable solutions that satisfy and benefit countries with rich biolgical diversity and chemical discovery programs.

Sequoia rapidly produces natural product compound libraries for biological screening by pharmaceutical, biotechnology, and agrochemical discovery programs. Sequoia is extracting samples using rapid purification and fractionation processes to provide corporate partners with diverse, novel molecules with selective biological activity. Each plant sample is carefully fractionated to yield single compounds, or groups of related compounds, that can be screened individually. This precise approach, which produces libraries of hundreds of individual compounds from each plant sample, allows each compound to be evaluated without interference from other compounds, as usually occurs in crude extracts.

The evaluation of complex mixtures has two problems. First, the large number of compounds in any complex mixture may interfere with or mask the activity of others. And second, the vast majority of compounds in crude extracts are present at a very low concentration. Many of the compounds in a crude extract may be present at concentrations below the limits of detection of many bioassays. While advances in bioassay development, robotics, and informatics may seem to allow rapid evaluation of huge numbers of extracts, finding the needle in the haystack is as dependent on what is being screened as how it is being screened.

Recent development of automated chromatographic methods allows fractionation of crude extracts into libraries of pure compounds or small families of related compounds. Careful separation of complex mixtures into their individual constituent molecules will eliminate interference or masking of activity and will also allow adjustment of concentration prior to screening. Associating analytical data with each microtitre plate well will further assist the screening process, enabling rapid dereplication and prioritization of leads. Given modern screening capacity, evaluation of libraries generated in this way will likely yield many of the lead compounds in the second renaissance of plant natural products research. The development of this new technology will ensure that plant extracts can be evaluated one molecular entity at a time, rather than requiring a compound to register activity through the chemical noise of a crude extract, and it seems likely that screening in the future will be based on libraries assembled from natural products, rather than crude extracts of the species themselves.

In January 2000, MBG and Sequoia signed a collaborative agreement with Gabon's Centre National Recherche Scientifique et Technologique (CENAREST) to collect plant samples for commercial development. John Stone and Gretchen Walters are responsible for collecting specimens in Gabon and collaborate with botanists at the Herbier National du Gabon (LBV). In the first year of the program, they have collected over 600 samples for Sequoia and more than 400 vouchers for study and distribution to herbaria throughout the world. Field efforts have focused on regions with few collections and areas in need of botanical inventories.

One of Missouri Botanical Garden's roles will be to work with source countries in conducting biological inventories of high interest regions in order to further research and conservation goals.

Sequoia Sciences and MBG are seeking corporate partners who desire interesting, biologically active compounds from plants. We provide a complete set of solutions for the operational challenges that have existed while working with plants.

• International collection agreements executed between each source country, MBG, and Sequoia.
• Plants collected by a bioprospecting team of MBG/Sequoia taxonomists and local botanists.
• Voucher specimens of all plants deposited in the MBG and source country herbaria.
• Dereplicated plant compounds in microtiter plates.
• Rapid isolation and characterization of compounds.
• Committed resupply.
• Alternative scale-up issues addressed.

Contact Information:

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 P.O. Box 299, St. Louis, MO 63166-0299
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