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


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Date

2020-11-18

Publication Type

Journal Article

ETH Bibliography

yes

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Data

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.

Publication status

published

Editor

Book title

Volume

7 (22)

Pages / Article No.

2001970

Publisher

Wiley

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

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); FANCD2-associated nuclease 1 (FAN-1); Phosphatidylinositol 3-kinase (PI3K)

Organisational unit

03463 - Neri, Dario (ehemalig) / Neri, Dario (former) check_circle
08641 - Scheuermann, Jörg (Tit.-Prof.) / Scheuermann, Jörg (Tit.-Prof.)

Notes

Funding

182003 - Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature (SNF)
670603 - Fulfilling Paul Ehrlich’s Dream: therapeutics with activation on demand (EC)
115766 - Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery (EC)

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