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Publication 109  

  1. DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules
    J.-P. Daguer, C. Zambaldo, M. Ciobanu, P. Morieux, S. Barluenga, N. Winssinger
    Chem. Sci. 2015, 6, 739-744

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

DOI: 10.1039/C4SC01654H 

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