The Application of DNA-templated Libraries in Drug Discovery

At Ensemble, the basic framework of the technology has not changed, but the company has implemented more sophisticated computational, experimental and instrumental tools to expand the applicability of DPC into previously difficult to access chemical structures, to increase the scale of a DPC library to hundreds of thousands of compounds, and to enhance the selection and hit identification throughputs. 

Even though individual macrocycle molecules can be feasibly synthesized from their linear precursors via macrocyclization reactions, large collections 

In the first selection campaign, a small number of compounds ( 0.02%) were identified as active hits against Bcl-xL. The top 10 hits have an enrichment 

A few important control experiments further validated the identified hit compounds. First, with the same library, a selection against an immobilized but denatured Bcl-xL did not generate the hits observed in the native Bcl-xL selection, indicating that hit compounds require active form of Bcl-xL. In the second control, addition of free BAK BH3 peptide was found to suppress hits. 

As a solution to this problem, Harbury and co-workers developed a method to physically partition DNA template pool into sub-population on individual 

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