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Evolution of chemistry and selection technology for DNA-encoded library
Peixiang Ma1, Shuning Zhang1,2, Qianping Huang2
1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
Acta Pharmaceutica Sinica. B
|February 7, 2024
Summary
DNA-encoded chemical libraries (DEL) evolve like biological systems using a chemical central dogma. Advances in DEL synthesis and selection strategies accelerate drug discovery through in vitro chemical evolution.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Synthetic Biology
Background:
- DNA-encoded chemical libraries (DEL) integrate genetics with chemical synthesis.
- DEL technology enables the creation of vast, diverse chemical spaces.
- The DEL system mimics biological evolution through a chemical central dogma.
Purpose of the Study:
- To review recent advancements in DEL synthetic methodologies.
- To summarize novel panning strategies for DEL-based screening.
- To highlight the potential of DEL in accelerating drug discovery.
Main Methods:
- Utilizing Polymerase Chain Reaction (PCR) for DNA amplification.
- Employing DNA sequencing to transcribe genetic information.
- Developing DNA-compatible synthesis for chemical phenotype generation.
Main Results:
- Expansion of the DEL synthetic toolbox.
- Development of evolution-driven selection systems for chemical evolution.
- Demonstration of in vitro evolution of chemicals via DEL.
Conclusions:
- DNA-compatible synthesis is crucial for expanding DEL chemical space.
- DEL offers a powerful platform for drug discovery through chemical evolution.
- Recent advances pave the way for harnessing DEL in pharmaceutical research.
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