Reversible Covalent Headpiece Enables Interconversion between Double‐ and Single‐Stranded DNA‐Encoded Chemical Libraries. (23rd December 2021)

• Record Type: Journal Article
• Authors: Zhao, Guixian; Zhong, Shuting; Zhang, Gong; Li, Yangfeng; Li, Yizhou
• Is Part Of: Angewandte Chemie. Volume 134:Number 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-23
• Subjects: DNA -- DNA-encoded library -- Drug discovery -- Photo-crosslinking -- Selection; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202115157
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : A novel DNA‐encoded chemical library (DEL) encoding method featuring a "reversible covalent headpiece (RCHP)" is described, which allows efficient interconversion between double‐ and single‐stranded DNA forms. Hybridization and covalent crosslinking of ssDEL with diversified complementary functionalized DNAs enables multiple DEL applications.