High-Throughput Solid-Phase Building Block Synthesis for DNA-Encoded Libraries.

Herein we provide a generalizable method for the cost-effective synthesis of thousands of building blocks (BBs) employing DNA-incompatible chemistries. The ability to produce large numbers of crude products via solid-phase synthesis has existed for decades; however, our work demonstrates a practical use of such crude reaction mixtures and employs DNA-conjugation to simultaneously encode, purify, and rapidly analyze the desired products. This workflow generated sp3-rich BBs that could be encoded by DNA in a high-throughput manner.