Seamless Bead to Microarray Screening: Rapid Identification of the Highest Affinity Protein Ligands from Large Combinatorial Libraries

SummarySeveral approaches have been developed for screening combinatorial libraries or collections of synthetic molecules for agonists or antagonists of protein function, each with its own advantages and limitations. In this report, we describe an experimental platform that seamlessly couples massively parallel bead-based screening of one-bead one-compound combinatorial libraries with microarray-based quantitative comparisons of the binding affinities of the many hits isolated from the bead library. Combined with other technical improvements, this technique allows the rapid identification of the best protein ligands in combinatorial libraries containing millions of compounds without the need for labor-intensive resynthesis of the hits.

► Experimental platform couples parallel bead-based screening with microarray-based comparisons of hit compounds ► Beads displaying hit compounds are non-covalently magnetized for rapid isolation from millions of non-hit beads ► Selectively cleavable linkers allow direct attachment of compounds from hit beads to microarrays without re-synthesis ► Method decreases the time and effort required for isolating and characterizing protein ligands