Design, Preparation, and Selection of DNA-encoded Dynamic Libraries

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2017 Aug 1

PMID 28757982

Citations 17

Authors

Gang Li

Wenlu Zheng

Zitian Chen

Yu Zhou

Yu Liu

Junrui Yang

Yanyi Huang

Xiaoyu Li

Affiliations

Soon will be listed here.

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.

Citing Articles

Protein-templated ligand discovery via the selection of DNA-encoded dynamic libraries.

Zhou Y, Shen W, Gao Y, Peng J, Li Q, Wei X Nat Chem. 2024; 16(4):543-555.

PMID: 38326646 DOI: 10.1038/s41557-024-01442-y.

A DNA-encoded chemical library based on chiral 4-amino-proline enables stereospecific isozyme-selective protein recognition.

Oehler S, Lucaroni L, Migliorini F, Elsayed A, Prati L, Puglioli S Nat Chem. 2023; 15(10):1431-1443.

PMID: 37400597 DOI: 10.1038/s41557-023-01257-3.

Trio-pharmacophore DNA-encoded chemical library for simultaneous selection of fragments and linkers.

Cui M, Nguyen D, Gaillez M, Heiden S, Lin W, Thompson M Nat Commun. 2023; 14(1):1481.

PMID: 36932079 PMC: 10023787. DOI: 10.1038/s41467-023-37071-1.

Exploring the Structural Diversity of DNA Bottlebrush Polymers Using an Oligonucleotide Macromonomer Approach.

Lu H, Cai J, Fang Y, Ren M, Tan X, Jia F Macromolecules. 2022; 55(6):2235-2242.

PMID: 36187461 PMC: 9521811. DOI: 10.1021/acs.macromol.1c02624.

Recent advances in DNA-encoded dynamic libraries.

Shi B, Zhou Y, Li X RSC Chem Biol. 2022; 3(4):407-419.

PMID: 35441147 PMC: 8985084. DOI: 10.1039/d2cb00007e.

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