omation mbers - Society for Laboratory Automation and Screening

4:00 pm Tuesday, February 3 HT Chemistry Room B3
Wim Meutermans
Alchemia Pty Ltd
P.O. Box 6242
Upper Mt. Gravatt
Queensland, 4122 Australia
wmeutermans@alchemia.com.au
Tailoring Molecular Diversity Through Carbohydrate-based Scaffolds
VAST drug discovery technology makes use of 3D scaffolds which resemble monosaccharides in structure and
where pharmacophoric substituents are readily attached at up to five positions in a regio- and stereo-controlled
manner. Conformationally rigid products, each with a unique 3D presentation, are produced in parallel using
automated techniques, thereby generating libraries of tailored structural and functional diversity. The nature of
the scaffold and substituents are modeled and designed to selectively target receptors, but also to optimize
ADME properties. Research that resulted in the identification of novel VAST drug leads for selected targets will
be presented, including diversity and modeling considerations, along with ‘in vitro’ and ‘in vivo’ data on activity,
toxicity and pharmacokinetics.
4:30 pm Tuesday, February 3 HT Chemistry Room B3
Jan Marik
University of California, Davis – Cancer Center
4501 X Street
Sacramento, California 95817
jmarik@ucdavis.edu
From “One-Bead One-Compound” to Chemical Microarrays
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Co-Author(s)
Aimin Song, Ruiwu Liu,
Xiaobing Wang, Alan Lehman,
Kit S. Lam
The era of combinatorial chemistry libraries began with spatially addressable low density arrays like the multipin
system described by Geysen and the spot synthesis of method published by Frank. At the same time, Fodor
et al. reported the light directed synthesis of the first spatially addressable high density chemical microarrays. In
1991, Lam et al. invented the “one-bead one-compound” (OBOC) method for highly efficient synthesis of random
peptide libraries containing millions of peptide beads, such that each bead displays only one peptide entity.
This OBOC library could be also viewed as an ultra high density peptide microarray that is spatially separable
but not addressable. In the last 10 years the OBOC method has been used to prepare encoded small molecule
libraries. Although huge number of compounds can be prepared with the OBOC method, only limited amounts of
compound can be retrieved from one single bead. To increase the capacity of each bead, Schreiber et al. reported
the use of macrobeads that can provide up to 0.5 mmol/bead of compound. In our lab we have recently developed
the one-aggregate one-compound method which has the capacity of generating 1 – 10 mmol of compound
from each aggregate. By applying the “split mix synthesis” approach, a large number of encoded compoundaggregates
can be generated efficiently. The bead aggregates consist of two populations of beads. The majority
of the beads have cleavable linkers and are used for preparation of the testing compound, whereas the minority
population of beads is colored and is used for the preparation of the encoding tag. After synthesis, the testing
compound is released to the solution from the aggregate and can be fed into the standard solution phase high
throughput screen, or selectively ligated to a biopolymer and printed to solid support to form a microarray. Positive
spots or wells can be traced back to the aggregate where the encoding beads can be retrieved for decoding.