DNA-encoded Library Synthesis

DNA-encoded libraries technology is a game changing innovation in drug discovery. DEL allows the synthesis and screening of millions, or even billions, of encoded compounds more quickly and cheaply than when using conventional methods. 

HitGen has developed a complete set of DEL production processes and quality control methods, which ensures the DELs are always constructed with higher efficiency and quality.

Production process 

HitGen uses the “split & pool” synthesis strategy to build all their DNA-encoded libraries. A building block (BB), such as an amino acid, is tagged with a DNA sequence. Then a second BB is added, and the DNA tag is lengthened with a sequence that corresponds to the second BB. Compounds of up to four BBs can be assembled. At each step, the BBs and tags are added to mixtures of thousands of different tagged BBs to quickly grow libraries to vast sizes. All the BBs at HitGen are validated to get the yields and by-product analysis under certain conditions in the model system. Only building blocks which meet the criteria are selected for DEL production. 

Quality control 

During the process of DEL production, HitGen uses different quality control methods (UPLCMS, HPLC and electrophoresis) to monitor chemistry or ligation reaction. HitGen will evaluate the quality of the final product using quality control methods developed in-house, such as electrophoresis and quantification (by Qubit, OD, bioanalyzer and qPCR).

Automation of DEL synthesis

A DNA-encoded library with high diversity usually requires large numbers of parallel reactions and 'split & pool' operations. The efficiency and homogeneity of these operations will determine the physical quality of the DNA-encoded libraries (DELs). To ensure the library quality, HitGen has established an automatic synthesis platform for DNA-encoded library synthesis.