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

  • Jacques Saarbach
  • Sofia Barluenga
  • Nicolas WinssingerEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 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.

Key words

Peptide nucleic acid (PNA) PNA-encoded synthesis (PES) DNA assemblies Microarray Selection Screening Binder Inhibitor 

Notes

Acknowledgments

We gratefully acknowledge the funding agencies which have supported this work (Swiss National Science Foundation, NCCR Chemical Biology) and the collaborators that have contributed to the development of PNA-encoded technologies.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Jacques Saarbach
    • 1
  • Sofia Barluenga
    • 1
  • Nicolas Winssinger
    • 1
    Email author
  1. 1.Department of Organic Chemistry, NCCR Chemical BiologyUniversity of GenevaGenevaSwitzerland

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