DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical world.In analogy with the biological world,the DEL world can evolv...DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical world.In analogy with the biological world,the DEL world can evolve by using a chemical central dogma,wherein DNA replicates using the PCR reactions to amplify the genetic codes,DNA sequencing transcripts the genetic information,and DNA-compatible synthesis translates into chemical phenotypes.Importantly,DNA-compatible synthesis is the key to expanding the DEL chemical space.Besides,the evolution-driven selection system pushes the chemicals to evolve under the selective pressure,i.e.,desired selection strategies.In this perspective,we summarized recent advances in expanding DEL synthetic toolbox and panning strategies,which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.展开更多
基金Financial support was provided by the National Natural Science Foundation of China(grant numbers 22177073,21977070,21907085,and U19A2011)the Natural Science Foundation of Shanghai,China(grant numbers 21ZR1442900 and 23ZR1437600)+2 种基金the Natural Science Foundation of Zhejiang Province,China(grant number LY22H300001)Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal SystemShanghai Key Laboratory of Orthopedic Implants(grant number KFKT202207,China)for financial support.
文摘DNA-encoded chemical library(DEL)links the power of amplifiable genetics and the nonself-replicating chemical phenotypes,generating a diverse chemical world.In analogy with the biological world,the DEL world can evolve by using a chemical central dogma,wherein DNA replicates using the PCR reactions to amplify the genetic codes,DNA sequencing transcripts the genetic information,and DNA-compatible synthesis translates into chemical phenotypes.Importantly,DNA-compatible synthesis is the key to expanding the DEL chemical space.Besides,the evolution-driven selection system pushes the chemicals to evolve under the selective pressure,i.e.,desired selection strategies.In this perspective,we summarized recent advances in expanding DEL synthetic toolbox and panning strategies,which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.