DNA-encoded chemical libraries



DNA-encoded chemical library (DECL) technology is used by the pharmaceutical industry to discover small molecules capable of modulating biologically relevant targets. DECL synthesis starts with an oligonucleotide that contains a chemical linker moiety, and proceeds through iterative cycles of DNA barcode elongation and chemical synthesis. DECL selections require little protein, minimal assay development and no specialized instrumentation. Parallel DECL selections can be easily conducted, making it possible to directly compare results across different conditions. The acquisition of building blocks is a large impediment when setting up a successful DECL platform. A potential solution is the sharing of building blocks between different labs, or the high-throughput parallel synthesis of novel building blocks. DNA-compatible reactions are required to join the building blocks together, and numerous academic labs have recently taken up this challenge. DECLs exist as unpurified mixtures, complicating data analysis. Machine learning may provide an improved ability to interrogate these data. DECL selections are largely limited to soluble purified proteins. However, progress has been made towards cell surface and in-cell selections. Publication guidelines are needed to better enable reproducibility; for example, the quantification of amplifiable DNA by quantitative PCR, and more complete datasets and building block lists, should be provided.

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