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Strategies for developing DNA-encoded libraries beyond binding assays

Yiran Huang, +2 more
- 01 Feb 2022 - 
- Vol. 14, Iss: 2, pp 129-140
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TLDR
The recent progress in using DNA-encoded chemical libraries to interrogate complex biological targets and their potential to identify structures that elicit function or possess other useful properties are discussed.
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This article is published in Nature Chemistry.The article was published on 2022-02-01. It has received 31 citations till now. The article focuses on the topics: Medicine & Drug discovery.

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Journal ArticleDOI

Visible Light-Promoted Divergent Benzoheterocyclization from Aldehydes for DNA-Encoded Chemical Libraries.

TL;DR: A visible light-promoted divergent synthesis of on-DNA benzoheterocycles from aldehydes is presented, demonstrating the feasibility of this approach in DNA-encoded chemical library construction.
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Converting Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded Libraries for More Versatile Selections

TL;DR: It is shown that dsD ELs could be efficiently converted to ssDELs and used for affinity-based selections either with purified proteins or on live cells.
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Vinyl azide as a synthon for DNA-compatible divergent transformations into N-heterocycles.

TL;DR: A series of DNA-compatible transformations utilizing on-DNA vinyl azide as a synthon to forge divergent N-heterocyclic scaffolds are developed to demonstrate the feasibility of these N- heterocycle syntheses in DNA-encoded chemical library construction.
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Metal‐Free and Open‐Air Arylation Reactions of Diaryliodonium Salts for DNA‐Encoded Library Synthesis

TL;DR: The use of “substrate activation” approach to address the arylation of DNA‐conjugated phenols is described and the new on‐DNA diaryliodonium salts chemistry affords a greater flexibility in DEL design and synthesis.
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DNA-Encoded Libraries: Towards Harnessing their Full Power with Darwinian Evolution.

TL;DR: A review of technologies that enable the translation of the genetic tag into synthetic molecules, both biochemically and chemically, and explore how it can be used to harness Darwinian evolutionary pressure can be found in this article .
References
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Journal ArticleDOI

Phage antibodies: filamentous phage displaying antibody variable domains

TL;DR: It is shown that complete antibody V domains can be displayed on the surface of fd bacteriophage, that the phage bind specifically to antigen and that rare phage can be isolated after affinity chromatography.
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Yeast surface display for screening combinatorial polypeptide libraries

TL;DR: C-terminal fusion to the Aga2p mating adhesion receptor of Saccharomyces cerevisiae has been used for the selection of scFv antibody fragments with threefold decreased antigen dissociation rate from a randomly mutated library.
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In vitro selection and evolution of functional proteins by using ribosome display.

TL;DR: Libraries of native folded proteins can now be screened and made to evolve in a cell-free system without any transformation or constraints imposed by the host cell.
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Encoded combinatorial chemistry.

TL;DR: The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening that can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library.
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