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However, little work has focused on the development of SMMs as analytical tools for biological research ( 14– 16), with the notable exception of peptide arrays as tools for determining the substrate preferences for proteases and other protein-modifying enzymes ( 12, 17– 21) and the binding preferences of antibodies ( 22– 24). Alternatively, methods exist for the synthesis of certain classes of compounds in situ on the array surface ( 6– 10).īy far the most common application of SMMs has been as a versatile platform for library screening, usually with the goal of identifying small-molecule ligands for a given protein of interest ( 1, 11– 13). The resulting solutions then are spotted robotically onto a chemically modified glass slide such that the library-derived molecule is attached covalently to the surface. These arrays are generally produced by first synthesizing a combinatorial library on a suitable bead resin, separating the beads into the wells of microtiter plates, and then releasing the compounds from the beads ( 4, 5). Small-molecule microarrays (SMMs) ( 1– 3) are becoming increasingly important tools in combinatorial chemistry.