Toward Larger Chemical Libraries: Encoding with Fluorescent Colloids in Combinatorial Chemistry

Abstract

Chemical library technology plays a central role in research areas such as drug discovery and gene screening.1 The most powerful combinatorial library synthesis method is the iterative “split and mix” synthesis on insoluble microscopic beads.2 This technique is an efficient method for accessing all combinations of chosen monomers such as nucleic acids, amino acids, or sugars in a small number of reactions. Compound identification from such large pools of compounds, be it bound to resin (one compound per bead) or in solution, is achieved through covalent attachment of molecular tags to the beads3 or through iterative deconvolution technologies.4 Herein we introduce an encoding method that involves physically attaching fluorescent colloidal particles (“reporters”) to the surface of solid support beads during split and mix syntheses, to produce an information-rich, colored barcode that can be easily, rapidly, and inexpensively decoded using fluorescence microscopy. This “colloidal barcoding” technique eliminates the need for compatible tagging chemistry in conventional molecular tagging3 or optical encoding5 procedures and permits unambiguous identification of compounds in libraries of any size and type.