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DNA-encoded chemical libraries (DEL) is a technology for the synthesis and screening of collections of small molecule compounds of unprecedented size. DEL is used in medicinal chemistry to bridge the fields of combinatorial chemistry and molecular biology. The aim of DEL technology is to accelerate the drug discovery process and in particular early phase discovery activities such as target validation and hit identification. DEL technology involves the conjugation of chemical compounds or building blocks to short DNA fragments that serve as identification bar codes and in some cases also direct and control the chemical synthesis. The technique enables the mass creation and interrogation of libraries via affinity selection, typically on an immobilized protein target. A homogeneous method for screening DNA-encoded libraries has recently been developed which uses water-in-oil emulsion technology to isolate, count and identify individual ligand-target complexes in a single-tube approach. In contrast to conventional screening procedures such as high-throughput screening, biochemical assays are not required for binder identification, in principle allowing the isolation of binders to a wide range of proteins historically difficult to tackle with conventional screening technologies. So, in addition to the general discovery of target specific molecular compounds, the availability of binders to pharmacologically important, but so-far “undruggable” target proteins opens new possibilities to develop novel drugs for diseases that could not be treated so far. In eliminating the requirement to initially assess the activity of hits it is hoped and expected that many of the high affinity binders identified will be shown to be active in independent analysis of selected hits, therefore offering an efficient method to identify high quality hits and pharmaceutical leads. == DNA-encoded chemical libraries and display technologies == Until recently, the application of molecular evolution in the laboratory had been limited to display technologies involving biological molecules, where small molecules lead discovery was considered beyond this biological approach. DEL has opened the field of display technology to include non-natural compounds such as small molecules, extending the application of molecular evolution and natural selection to the identification of small molecule compounds of desired activity and function. DNA encoded chemical libraries bear resemblance to biological display technologies such as antibody phage display technology, yeast display, mRNA display and aptamer SELEX. In antibody phage display, antibodies are physically linked to phage particles that bear the gene coding for the attached antibody, which is equivalent to a physical linkage of a “phenotype” (the protein) and a “genotype” (the gene encoding for the protein ). Phage-displayed antibodies can be isolated from large antibody libraries by mimicking molecular evolution: through rounds of selection (on an immobilized protein target), amplification and translation. In DEL the linkage of a small molecule to an identifier DNA code allows the facile identification of binding molecules. DEL libraries are subjected to affinity selection procedures on an immobilized target protein of choice, after which non-binders are removed by washing steps, and binders can subsequently be amplified by polymerase chain reaction (PCR) and identified by virtue of their DNA code (e.g.by DNA sequencing). In evolution-based DEL technologies (see below) hits can be further enriched by performing rounds of selection, PCR amplification and translation in analogy to biological display systems such as antibody phage display. This makes it possible to work with much larger libraries. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「DNA-encoded chemical library」の詳細全文を読む スポンサード リンク
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