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High-Density DNA and RNA microarrays - Photolithographic Synthesis, Hybridization and Preparation of Large Nucleic Acid Libraries
Published on: August 12, 2019
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Photochemical Methods Applied to DNA Encoded Library (DEL) Synthesis
Bianca Matsuo1, Albert Granados1, Guillaume Levitre1
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania19104-6323, United States.
Accounts of Chemical Research
|January 19, 2023
Summary
DNA-encoded library technology (DELT) uses DNA tags to rapidly screen billions of molecules for drug discovery. Visible-light photocatalysis offers a powerful, DNA-compatible method to expand chemical diversity in DELT screening.
Area of Science:
- Medicinal Chemistry
- Chemical Biology
- Drug Discovery Technologies
Background:
- DNA-encoded library technology (DELT) integrates chemical synthesis with DNA sequencing for efficient screening of vast compound libraries.
- Traditional DELT methods face challenges with DNA integrity due to harsh reaction conditions.
- Photocatalysis offers mild, efficient reaction conditions suitable for on-DNA synthesis.
Purpose of the Study:
- To review recent advances in visible-light-driven photocatalysis for DNA-encoded library synthesis.
- To highlight the compatibility of photocatalytic methods with DNA integrity.
- To showcase the expansion of chemical space accessible through on-DNA photocatalytic diversification.
Main Methods:
- Utilizing visible-light photocatalysis to perform chemical transformations on DNA-linked building blocks.
- Employing split-and-pool synthesis to create large combinatorial libraries on DNA.
- Applying polymerase chain reaction (PCR) and next-generation sequencing (NGS) for library readout.
Main Results:
- Photocatalytic reactions enable efficient bond formation under mild conditions, preserving DNA integrity.
- Visible-light-driven reactions expand the range of chemical building blocks that can be synthesized on-DNA.
- A comprehensive table of reported photoinduced methods for DELT is provided, detailing scope, applications, and DNA compatibility.
Conclusions:
- Visible-light photocatalysis is a powerful and DNA-compatible approach for advancing DNA-encoded library technology.
- This methodology significantly enhances the efficiency and scope of DELT for drug discovery.
- The presented advances provide compelling rationale for adopting photocatalytic methods in DELT applications.
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