On the design of lead-like DNA-encoded chemical libraries

DNA-encoded libraries (DELs) are becoming an established technology for finding ligands for protein targets. We have abstracted and analysed libraries from the literature to assess the synthesis strategy, selections of reactions and monomers and their propensity to reveal hits. DELs have led to hit compounds across a range of diverse protein classes. The range of reactions and monomers utilised has been relatively limited and the hits are often higher in molecular weight than might be considered ideal. Considerations for future library designs with reference to chemical diversity and lead-like properties are discussed.

Automated summary

DNA-encoded libraries (DELs) have become an established technology for finding ligands for protein targets and have led to hit compounds across diverse protein classes. However, the range of reactions and monomers utilized is relatively limited and the hit compounds are often higher in molecular weight than ideal. Considerations for future library designs include chemical diversity and lead-like properties.