Design, preparation, and selection of DNA-encoded dynamic libraries

被引：54

作者：

Li, Gang ^{[1
]}

Zheng, Wenlu ^{[2
]}

Chen, Zitian ^{[3
,4
]}

Zhou, Yu ^{[2
]}

Liu, Yu ^{[1
]}

Yang, Junrui ^{[3
,4
]}

Huang, Yanyi ^{[3
,4
]}

Li, Xiaoyu ^{[1
,2
]}

机构：

[1] Peking Univ, Key Lab Bioorgan Chem & Mol Engn, BNLMS, Minist Educ,Coll Chem & Mol Engn, Beijing 100871, Peoples R China

[2] Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Key Lab Chem Genom, Shenzhen 518055, Peoples R China

[3] Peking Univ, Biodynam Opt Imaging Ctr BIOPIC, Beijing 100871, Peoples R China

[4] Peking Univ, Coll Engn, Beijing 100871, Peoples R China

来源：

CHEMICAL SCIENCE | 2015年 / 6卷 / 12期

基金：

国家教育部博士点专项基金资助;

关键词：

LIGAND-TARGET PAIRS; PHOTO-CROSS-LINKING; IN-VITRO SELECTION; COMBINATORIAL LIBRARIES; PROTEIN RECOGNITION; CHEMICAL LIBRARIES; RECEPTOR LIGANDS; SMALL MOLECULES; DISCOVERY; INHIBITORS;

D O I：

10.1039/c5sc02467f

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：7097 / 7104

页数：8

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