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Scientific article
English

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

Published inChemical science, vol. 6, no. 1, p. 739-744
Publication date2015
Abstract

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.

Citation (ISO format)
DAGUER, Jean Pierre et al. DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules. In: Chemical science, 2015, vol. 6, n° 1, p. 739–744. doi: 10.1039/C4SC01654H
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ISSN of the journal2041-6520
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