A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks
Abstract A versatile and Lipinski‐compliant DNA‐encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB‐DEL library, constructed in single‐stranded DNA format, a...
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doaj-6523af672d2b411ba7e7080f84e454922020-11-25T04:10:44ZengWileyAdvanced Science2198-38442020-11-01722n/an/a10.1002/advs.202001970A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building BlocksGabriele Bassi0Nicholas Favalli1Miriam Vuk2Marco Catalano3Adriano Martinelli4Anika Trenner5Antonio Porro6Su Yang7Chuin Lean Tham8Mustafa Moroglu9Wyatt W. Yue10Stuart J. Conway11Peter K. Vogt12Alessandro A. Sartori13Jörg Scheuermann14Dario Neri15Department of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandDepartment of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandDepartment of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandDepartment of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandDepartment of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandInstitute of Molecular Cancer Research University of Zürich Zürich 8006 SwitzerlandInstitute of Molecular Cancer Research University of Zürich Zürich 8006 SwitzerlandScripps Research Institute Department of Molecular Medicine La Jolla CA 92037 USAStructural Genomic Consortium (SGC) Nuffield Department of Medicine University of Oxford Oxford OX1 2JD UKDepartment of Chemistry Chemistry Research Laboratory University of Oxford Mansfield Road Oxford OX1 3TA UKStructural Genomic Consortium (SGC) Nuffield Department of Medicine University of Oxford Oxford OX1 2JD UKDepartment of Chemistry Chemistry Research Laboratory University of Oxford Mansfield Road Oxford OX1 3TA UKScripps Research Institute Department of Molecular Medicine La Jolla CA 92037 USAInstitute of Molecular Cancer Research University of Zürich Zürich 8006 SwitzerlandDepartment of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandDepartment of Chemistry and Applied Biosciences ETH Zürich Zürich 8092 SwitzerlandAbstract A versatile and Lipinski‐compliant DNA‐encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB‐DEL library, constructed in single‐stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single‐stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self‐assembled selectable chemical structures, leading to the identification of affinity‐matured compounds.https://doi.org/10.1002/advs.202001970Human alpha‐aminoadipic semialdehyde synthase (AASS)affinity maturationcyclic‐AMP response element binding protein (CREBBP)DNA‐encoded chemical libraries (DEL)drug discoveryencoded self‐assembling chemical libraries (ESAC) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gabriele Bassi Nicholas Favalli Miriam Vuk Marco Catalano Adriano Martinelli Anika Trenner Antonio Porro Su Yang Chuin Lean Tham Mustafa Moroglu Wyatt W. Yue Stuart J. Conway Peter K. Vogt Alessandro A. Sartori Jörg Scheuermann Dario Neri |
spellingShingle |
Gabriele Bassi Nicholas Favalli Miriam Vuk Marco Catalano Adriano Martinelli Anika Trenner Antonio Porro Su Yang Chuin Lean Tham Mustafa Moroglu Wyatt W. Yue Stuart J. Conway Peter K. Vogt Alessandro A. Sartori Jörg Scheuermann Dario Neri A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks Advanced Science Human alpha‐aminoadipic semialdehyde synthase (AASS) affinity maturation cyclic‐AMP response element binding protein (CREBBP) DNA‐encoded chemical libraries (DEL) drug discovery encoded self‐assembling chemical libraries (ESAC) |
author_facet |
Gabriele Bassi Nicholas Favalli Miriam Vuk Marco Catalano Adriano Martinelli Anika Trenner Antonio Porro Su Yang Chuin Lean Tham Mustafa Moroglu Wyatt W. Yue Stuart J. Conway Peter K. Vogt Alessandro A. Sartori Jörg Scheuermann Dario Neri |
author_sort |
Gabriele Bassi |
title |
A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks |
title_short |
A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks |
title_full |
A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks |
title_fullStr |
A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks |
title_full_unstemmed |
A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks |
title_sort |
single‐stranded dna‐encoded chemical library based on a stereoisomeric scaffold enables ligand discovery by modular assembly of building blocks |
publisher |
Wiley |
series |
Advanced Science |
issn |
2198-3844 |
publishDate |
2020-11-01 |
description |
Abstract A versatile and Lipinski‐compliant DNA‐encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB‐DEL library, constructed in single‐stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single‐stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self‐assembled selectable chemical structures, leading to the identification of affinity‐matured compounds. |
topic |
Human alpha‐aminoadipic semialdehyde synthase (AASS) affinity maturation cyclic‐AMP response element binding protein (CREBBP) DNA‐encoded chemical libraries (DEL) drug discovery encoded self‐assembling chemical libraries (ESAC) |
url |
https://doi.org/10.1002/advs.202001970 |
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