PMID: 9427662Mar 7, 1998Paper

A miniaturized arrayed assay format for detecting small molecule-protein interactions in cells

Chemistry & Biology
A J YouS L Schreiber

Abstract

Two complementary approaches to studying the cellular function of proteins involve alteration of function either by mutating protein-encoding genes or by binding a small molecule to the protein. A mutagen can generate millions of genetic mutations; correspondingly, split-pool synthesis can generate millions of unique ligands attached to individual beads. Genetic screening of mutations is relatively straightforward but, in contrast, split-pool synthesis presents a challenge to current methods of screening for compounds that alter protein function. The methods used to screen natural products are not feasible for large libraries composed of covalently immobilized compounds on synthesis beads. The sheer number of compounds synthesized by split-pool synthesis, and the small quantity of individual compound attached to each bead require assay miniaturization for efficient screening. We present a miniaturized cell-based technique for the screening of ligands prepared by split-pool synthesis. Spatially defined droplets with uniform volumes of approximately 50-150 nanoliters (depending on well dimensions) are arrayed on plastic devices prepared using a combination of photolithography and polymer molding. Using this microtechnology, appro...Continue Reading

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Citations

Sep 1, 2000·Advanced Drug Delivery Reviews·N Hussain
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Oct 24, 1998·Bioorganic & Medicinal Chemistry·S L Schreiber
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Nov 23, 2021·ACS Chemical Biology·Wesley G CochraneBrian M Paegel

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