High Throughput Screening

A library of a billion or more different molecules is only useful if the molecules can be quickly and economically screened for the desired function. "High-throughput" techniques have been developed that automate most of the steps required to combine the molecules with their targets and evaluate the extent of any reaction.

Typically, the molecules are arrayed on a solid surface and the target is added. Unbound target is washed away. Fluorescent tags are often added to the target, to allow easy (and automated) visualization of the results. Robotic systems controlled by computers can react and evaluate billions of separate compounds in the time it would take a human to screen a dozen. One such approach is used in DNA microarrays, in which thousands of genes from a DNA library are attached to a solid base. These are reacted with messenger RNAs from a cell, and the results are visualized fluorescently.

Interaction of small molecules with target enzymes depends on shape and charge.

macromolecules large molecules such as proteins, carbohydrates, and nucleic acids enzyme a protein that controls a reaction in a cell template a master copy


A high-throughput screening assay can quickly assess the target-binding ability of millions of compounds.


In addition to its use in drug development, combinatorial chemistry can be applied to other areas of biomedical research, such as the design of molecules for diagnosing medical conditions. Compounds for these applications can be larger than pharmaceutical compounds, and do not have to be designed to enter the body. Using a novel combinatorial chemistry method called in vitro selection or SELEX (systematic evolution of ligands by exponential enrichment), a short DNA or RNA molecule (termed an oligonu-

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