Volume 134, Issue 7 e202115157
Forschungsartikel

Reversible Covalent Headpiece Enables Interconversion between Double- and Single-Stranded DNA-Encoded Chemical Libraries

Guixian Zhao

Guixian Zhao

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

These authors contribute equally to this work.

Search for more papers by this author
Shuting Zhong

Shuting Zhong

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

These authors contribute equally to this work.

Search for more papers by this author
Dr. Gong Zhang

Dr. Gong Zhang

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

Search for more papers by this author
Dr. Yangfeng Li

Dr. Yangfeng Li

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

Search for more papers by this author
Prof. Dr. Yizhou Li

Corresponding Author

Prof. Dr. Yizhou Li

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, 400044 Chongqing, P. R. China

Search for more papers by this author
First published: 13 December 2021
Citations: 3

Abstract

The use of a proper encoding methodology is one of the most important aspects when practicing DEL technology. A “headpiece”-based double-stranded DEL encoding method is currently the most widely used for productive DEL. However, the robustness of double-stranded DEL construction conflicts with the versatility presented by single-stranded DEL applications. We here report a novel encoding method, which is based on a “reversible covalent headpiece (RCHP)”. The RCHP allows reversible interconversion between double- and single-stranded DNA formats, providing an avenue to robust synthesis and allowing for the applications in distinct setups. We have validated the versatility of this encoding method with encoded self-assembled chemical library and DNA-encoded dynamic library technology. Notably, based on the RCHP-settled library construction, a unique “ternary covalent complex” mediating ligand isolation methodology against non-immobilized targets was developed.

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information of this article.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.