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Cropsolution’s resources and expertise can help you discover
and develop an agrochemical. We are ready to help with Biochemistry,
Molecular Biology, Chemical Synthesis/Analoging, Library Screening
or Biological Screening. Please contact us and we can develop
a special project for your company.
Biochemistry and Molecular Biology
Cropsolution’s Biochemistry and Molecular Biology team is located
at our North Carolina site. The NC site contains approximately
3000 sq. ft. of lab space and is well-equipped for modern research. The
major equipment includes an LC system for protein purification, a quantitative
pcr thermocycler, a phosphorimager, a plate-based scintillation counter,
a spectrophotometer, a multi-detection plate reader, high speed centrifuges,
incubators, growth chambers, and tissue culture hoods. The Biochemistry
and Molecular Biology team’s major responsibilities include target
identification, cloning, expression, purification, and characterization;
EC selections; mode-of-action studies; assay development; and in vitro
and in vivo characterization of leads.
Chemical synthesis
Six synthetic chemists and one analytical
chemist comprise the chemistry group, located in Mountain View, CA. Their primarily responsibilities
include the design and synthesis of novel hits/leads, chemical library
design, rehearsal and synthesis, and lead structure determination. The
members of the synthetic chemistry group possess a combined total of
over 80 years of agricultural chemical expertise, and have three commercial
products to their credit. Analytical support is provided by an analytical
chemist who has 20 years of experience. Her responsibilities include
operation and maintenance of Cropsolution’s state-of-the-art analytical
equipment for determining sample purity and elucidating chemical structure. On
site instrumentation includes LC/MS, LC/MS/MS, HPLC, Prep HPLC, and NMR.
Biological screening
Also at the Mountain View location is the biology group, whose
primary function is the biological evaluation of compounds on both in
vitro and in
vivo targets. The two Cropsolution biologists have a combined 11
years of experience in crop protection agrochemical screening. The group
has high throughput screening capabilities, with automated plate handling. All
screens are conducted in 96-well microtiter plates. In vivo plate
screens have been developed for all three indications: insecticides, herbicides,
and fungicides.
Four species of Lepidoptera are used in our insecticide screens: Spodoptera
exigua (beet armyworm), Spodoptera frugiperda (fall armyworm), Trichoplusia
ni (cabbage looper), and Helicoverpa zea (tomato fruitworm).
Six commercial insecticide standards are run concurrently with the experimental
compounds as internal controls for assay sensitivity and insect response. The
standards are listed in Table 1.

Three species of plants are used in our herbicide screens: Arabidopsis
thaliana, Agrostis sp. and Nicotinia tabacum (common
tobacco). Symptomology observed includes growth inhibition, bleaching,
leaf curling, and root growth inhibition. Six commercial herbicide
standards are run concurrently with the experimental compounds as internal
controls for assay sensitivity and plant response. The standards
are described in Table 2 with their biochemical mode of action.

We currently have the capability and are permitted by the federal government
to screen a number of representative fungal pathogens from ascomycetes,
basidiomycetes, deuteromycetes, and oomycetes. Our primary screen includes
the following pathogens: Botrytis cinerea (grey mold), Phytophthora
infestans (late blight), Stagnospora nodorum (glume blotch), Septoria
tritici (leaf blotch), and Ustilago maydis (corn smut).
At least six commercial fungicide standards are run concurrently with
the experimental compounds as internal controls for assay sensitivity
and pathogen response. The standards are described in Table 3 with
their biochemical mode of action.

Chemistry library
Cropsolution currently has a collection of over 110,000 compounds of diverse
structure. About 40,000 of these were synthesized by Cropsolution chemists
using both solution and solid phase synthetic methods. Scaffolds were designed
and building blocks and their substituents were selected based on agrochemical
considerations. Molecular weights of these compounds range from 250 to 500,
and their octanol/water partition coefficients (clog P values) are less than
5. Functionality conducive to phloem transport in the plant, e.g., weak acids,
has been incorporated into the design of some of these compounds in order
to increase the opportunity for systemic activity. A number of in vivo active
compounds have been identified from this part of the collection, affirming
its general utility as a source of hits/leads. Two of these hits have resulted
in compounds that demonstrate fungicidal or herbicidal activity in greenhouse
evaluations. The remainder of the collection, about 70,000 compounds, was
acquired from an outside source. These compounds were carefully selected
to complement the 40,000 compound collection. Again, diversity of structure
and favorable physicochemical properties for crop protection were important
criteria in their selection.
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