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DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules.
Journal article

DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules.

  • Daguer JP Department of Organic Chemistry , NCCR Chemical Biology , University of Geneva , Switzerland . Email: nicolas.winssinger@unige.ch.
  • Zambaldo C Department of Organic Chemistry , NCCR Chemical Biology , University of Geneva , Switzerland . Email: nicolas.winssinger@unige.ch.
  • Ciobanu M Institut de Science et Ingénierie Supramoléculaires (ISIS - UMR 7006) , Université de Strasbourg - CNRS , 8 allée Gaspard Monge , F67000 Strasbourg , France.
  • Morieux P Institut de Science et Ingénierie Supramoléculaires (ISIS - UMR 7006) , Université de Strasbourg - CNRS , 8 allée Gaspard Monge , F67000 Strasbourg , France.
  • Barluenga S Department of Organic Chemistry , NCCR Chemical Biology , University of Geneva , Switzerland . Email: nicolas.winssinger@unige.ch.
  • Winssinger N Department of Organic Chemistry , NCCR Chemical Biology , University of Geneva , Switzerland . Email: nicolas.winssinger@unige.ch.
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  • 2018-08-30
Published in:
  • Chemical science. - 2015
General Chemistry
English Fragment-based lead discovery has proven to be a powerful method in the drug discovery process. The combinatorial output that is accessible by combining fragments is very attractive; however, identifying fragment pairs that bind synergistically and linking them productively can be challenging. Several technologies have now been established to prepare and screen nucleic acid-encoded libraries (ssDNA, dsDNA, PNA), and it has been shown that pairs of molecules combined by hybridization can bind synergistically to a target. Herein we apply this concept to combinatorially pair two libraries of small molecule fragments, use the fittest fragments supplemented with closely related analogs to build a focused library covalently linking the fragments with different spacers, and apply this strategy to the discovery of a potent ligand for Hsp70.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/70369
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