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Issue 12, 2015
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Design, preparation, and selection of DNA-encoded dynamic libraries

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Abstract

We report a method for the preparation and selection of DNA-encoded dynamic libraries (DEDLs). The library is composed of two sets of DNA-linked small molecules that are under dynamic exchange through DNA hybridization. Addition of the protein target shifted the equilibrium, favouring the assembly of high affinity bivalent binders. Notably, we introduced a novel locking mechanism to stop the dynamic exchange and “freeze” the equilibrium, thereby enabling downstream hit isolation and decoding by PCR amplification and DNA sequencing. Our DEDL approach has circumvented the limitation of library size and realized the analysis and selection of large dynamic libraries. In addition, this method also eliminates the requirement for modified and immobilized target proteins.

Graphical abstract: Design, preparation, and selection of DNA-encoded dynamic libraries

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Publication details

The article was received on 08 júl. 2015, accepted on 09 sep. 2015 and first published on 11 sep. 2015


Article type: Edge Article
DOI: 10.1039/C5SC02467F
Citation: Chem. Sci., 2015,6, 7097-7104
  • Open access: Creative Commons BY license
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    Design, preparation, and selection of DNA-encoded dynamic libraries

    G. Li, W. Zheng, Z. Chen, Y. Zhou, Y. Liu, J. Yang, Y. Huang and X. Li, Chem. Sci., 2015, 6, 7097
    DOI: 10.1039/C5SC02467F

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