A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks

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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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2020-11-01
Series:Advanced Science
Subjects:
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)
Online Access:https://doi.org/10.1002/advs.202001970
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spelling 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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