High-throughput manual parallel synthesis using SynPhase crowns and lanterns |
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Authors: | Gerritz Samuel W Norman Mark H Barger Lee A Berman Judd Bigham Eric C Bishop Michael J Drewry David H Garrison Deanna T Heyer Dennis Hodson Stephen J Kakel Jennifer A Linn James A Marron Brian E Nanthakumar Suganthini S Navas Frank J |
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Affiliation: | Department of Medicinal Chemistry, GlaxoSmithKline Inc., Five Moore Drive, P.O. Box 13398, Research Triangle Park, North Carolina 27709, USA. samuel.gerritz@bms.com |
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Abstract: | The high-throughput manual solid-phase parallel synthesis of libraries comprising thousands of discrete samples using pellicular supports (i.e. SynPhase crowns and lanterns) and a suite of novel tools and techniques is described. Key aspects of this approach include the combination of a split-split-split synthesis strategy with spatial encoding to differentiate thousands of crowns, the rapid washing and filtration of up to 48 reaction vessels in parallel, the application of an inexpensive and environmentally friendly technique to remove trifluoroacetic acid from sixteen 96-well plates in parallel, and a high-throughput method for removing cleaved crowns from reusable pin racks. Tens of thousands of discrete samples have been produced in-house using this conceptually and operationally straightforward strategy. |
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