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Updated: Nov 5, 2025

High-Density DNA and RNA microarrays - Photolithographic Synthesis, Hybridization and Preparation of Large Nucleic Acid Libraries

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Developments in Photoredox-Mediated Alkylation for DNA-Encoded Libraries.

Shivani Patel¹, Shorouk O Badir¹, Gary A Molander¹

¹Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.

Trends in Chemistry

|May 14, 2021

Summary

DNA-encoded library (DEL) technology accelerates drug discovery by enabling large-scale screening of small organic ligands. Photoredox catalysis, particularly alkylation, is explored for novel scaffold construction in DEL synthesis.

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Area of Science:

Medicinal Chemistry
Organic Synthesis
Drug Discovery

Background:

DNA-encoded library (DEL) technology offers a powerful platform for discovering therapeutic candidates.
DELs enable cost-effective, time-efficient, large-scale assembly and screening of billions of ligands.
A key challenge in DEL synthesis is the requirement for water-compatible reactions under ambient conditions.

Purpose of the Study:

To critically discuss the validation of photoredox-mediated alkylation within DNA-encoded library environments.
To highlight current synthetic gaps in applying photoredox catalysis to DELs.
To speculate on future opportunities for advancing photoredox-mediated DEL synthesis.

Main Methods:

Review and critical discussion of existing literature on photoredox catalysis in DELs.
Focus on Ni-catalyzed manifolds and radical/polar crossover reactions.
Analysis of synthetic challenges and potential solutions for DEL applications.

Main Results:

Photoredox catalysis, including Ni-catalyzed reactions and radical/polar crossover, enables novel scaffold construction in DELs.
These methods utilize regulated odd-electron intermediates to access uncharted chemical space.
Validation of photoredox-mediated alkylation in DEL environments is a key focus.

Conclusions:

Photoredox-mediated alkylation presents a promising avenue for DEL synthesis, expanding accessible chemical space.
Addressing current synthetic gaps is crucial for broader adoption and development.
Further research is needed to fully realize the potential of photoredox catalysis in DEL technology for drug discovery.