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DNA Microarrays

DNA Microarrays

Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...

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Updated: Nov 26, 2025

Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens

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Published on: June 6, 2020

Scanning Protein Surfaces with DNA-Encoded Libraries.

Verena B K Kunig¹, Marco Potowski¹, Mateja Klika Škopić¹

¹Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227, Dortmund, Germany.

|December 9, 2020

Summary

DNA-encoded chemical libraries (DELs) enable scanning of protein surfaces for drug discovery. DEL screens identify protein-protein interaction inhibitors and surface binders for GPCRs and kinases, revealing novel chemotypes for drug development.

Keywords:

DNA-encoded libraries drug development peptidomimetics protein-protein interactions screening

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Area of Science:

Medicinal Chemistry
Drug Discovery
Chemical Biology

Background:

Understanding protein ligandability is crucial for drug development, particularly for targeting protein-protein interactions.
Protein surface binders are key for inhibiting interactions, necessitating methods to scan large chemical spaces on protein surfaces.

Purpose of the Study:

To explore the utility of DNA-encoded chemical libraries (DELs) for identifying novel protein surface binders.
To investigate diverse chemotypes, including peptides, peptidomimetics, and peptoids, within the DEL framework for drug discovery.

Main Methods:

Utilizing DNA-encoded chemical libraries (DELs) for high-throughput screening against protein targets.
Analyzing the chemical structures of identified binders, focusing on peptides, peptidomimetics, and exploring less-represented peptoid libraries.
Evaluating the potential of fragment-like starting points for developing more potent molecules.

Main Results:

DEL selection screens successfully identified inhibitors of protein-protein interactions and binders for G protein-coupled receptors (GPCRs) and kinases.
Predominant surface-binding chemotypes identified were chemically modified and cyclized peptides, along with functional small-molecule peptidomimetics.
Peptoid libraries and structural peptidomimetics represent less explored chemical space within DELs, suggesting opportunities for novel library designs.

Conclusions:

DELs are effective tools for scanning protein surfaces and identifying diverse drug-like compounds, including inhibitors of protein-protein interactions.
The study highlights the prevalence of peptide-based chemotypes from DELs and suggests expanding library design to include peptoids and peptidomimetics.
DEL technology demonstrates potential for evolving weak, fragment-like binders into more potent drug candidates.