DNA-Encoded Chemical Libraries: A Comprehensive Review with Succesful Stories and Future Challenges


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Date

2021-08-13

Publication Type

Review Article

ETH Bibliography

yes

Citations

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Abstract

DNA-encoded chemical libraries (DELs) represent a versatile and powerful technology platform for the discovery of small-molecule ligands to protein targets of biological and pharmaceutical interest. DELs are collections of molecules, individually coupled to distinctive DNA tags serving as amplifiable identification barcodes. Thanks to advances in DNA-compatible reactions, selection methodologies, next-generation sequencing, and data analysis, DEL technology allows the construction and screening of libraries of unprecedented size, which has led to the discovery of highly potent ligands, some of which have progressed to clinical trials. In this Review, we present an overview of diverse approaches for the generation and screening of DEL molecular repertoires. Recent success stories are described, detailing how novel ligands were isolated from DEL screening campaigns and were further optimized by medicinal chemistry. The goal of the Review is to capture some of the most recent developments in the field, while also elaborating on future challenges to further improve DEL technology as a therapeutic discovery platform.

Publication status

published

Editor

Book title

Volume

4 (4)

Pages / Article No.

1265 - 1279

Publisher

American Chemical Society

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

DNA-encoded libraries; affinity selections; next-generation sequencing; small molecules; machine learning

Organisational unit

03463 - Neri, Dario (ehemalig) / Neri, Dario (former) check_circle

Notes

Funding

163479 - Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature (SNF)
670603 - Fulfilling Paul Ehrlich’s Dream: therapeutics with activation on demand (EC)

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