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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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Supplementary files

Article information


Submitted
08 Jul 2015
Accepted
09 Sep 2015
First published
11 Sep 2015

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2015,6, 7097-7104
Article type
Edge Article
Author version available

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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