Psoralen as an interstrand DNA crosslinker in the selection of DNA-Encoded dynamic chemical library

Biochem Biophys Res Commun. 2020 Dec 3;533(2):215-222. doi: 10.1016/j.bbrc.2020.04.033. Epub 2020 Apr 29.

Abstract

DNA-encoded chemical library (DEL) has emerged as a powerful technology for ligand discovery in biomedical research. Recently, we have developed a DNA-encoded dynamic library (DEDL) approach by incorporating the concept of dynamic combinatorial library (DCL) with DELs. DEDL has shown excellent potential in ligand discovery towards a variety of protein targets. However, the requirement of having a pair of unnatural p-stilbazoles as the interstrand DNA crosslinker has limited the chemical diversity of DEDLs. Here, we replaced p-stilbazole with psoralen (PS) and tested the feasibility of psoralen as the crosslinker in DEDL selection. Since psoralen is commercially available and does not require any special crosslinking partner, existing DELs may be directly used to create high-diversity DEDLs. This study is expected to greatly facilitate the development of DEDLs as a versatile tool in drug discovery.

Keywords: DNA-Encoded chemical library; Drug discovery; Dynamic combinatorial library; High throughput screening; Psoralen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / chemistry*
  • DNA / chemical synthesis
  • DNA / chemistry*
  • Drug Discovery
  • Ficusin / chemical synthesis
  • Ficusin / chemistry*
  • Photochemical Processes
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry*

Substances

  • Cross-Linking Reagents
  • Small Molecule Libraries
  • DNA
  • Ficusin