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PNA-Encoded Synthesis (PES) and DNA Display of Small Molecule Libraries

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Published in Nielsen P. Peptide Nucleic Acids: Methods and Protocols. New York: Springer. 2020, p. 119-139
Collection Methods in Molecular Biology; 2105
Abstract DNA-encoded library technologies have emerged as a powerful platform to rapidly screen for binders to a protein of interest. These technologies are underpinned by the ability to encode a rich diversity of small molecules. While large libraries are accessible by cycles of mix and split synthesis, libraries based on single chemistries tend to be redundant. Furthermore, the quality of libraries generally decreases with the number of synthetic transformations performed in its synthesis. An alternative approach is to use hybridization to program the combinatorial assembly of fragment pairs onto a library of DNA templates. A broad molecular diversity is more easily sampled since it arises from the pairing of diverse fragments. Upon identification of productive fragment pairs, a focused library covalently linking the fragments is prepared. This focused library includes linker of different length and geometry and offers the opportunity to enrich the selected fragment set with close neighbors. Herein we describe detailed protocols to covalently link diverse fragments and screen fragment-based libraries using commercially available microarray platform.
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ISBN: 978-1-0716-0242-3
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Research group Groupe Winssinger
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SAARBACH, Jacques, BARLUENGA BADIOLA, Sofia, WINSSINGER, Nicolas. PNA-Encoded Synthesis (PES) and DNA Display of Small Molecule Libraries. In: Nielsen P. (Ed.). Peptide Nucleic Acids: Methods and Protocols. New York : Springer, 2020. p. 119-139. (Methods in Molecular Biology; 2105) doi: 10.1007/978-1-0716-0243-0_7 https://archive-ouverte.unige.ch/unige:139639

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Deposited on : 2020-08-17

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