DNA-encoded libraries via late-stage functionalization strategies: a review

Area of Science:

• Medicinal Chemistry
• Synthetic Chemistry
• Drug Discovery

Background:

• DNA-encoded libraries (DEL) represent a significant advancement in hit identification for drug discovery.
• Miniaturized assays facilitate high-throughput screening (HTS) against diverse biological targets.
• DEL technology offers access to vast chemical diversity for exploring novel molecular entities.

Purpose of the Study:

• To review metal-mediated synthetic pathways for late-stage functionalization of DNA strands.
• To analyze methods for accessing diverse DEL libraries.
• To critically evaluate the utility and limitations of these synthetic protocols.

Main Methods:

• Literature review of metal-mediated synthetic strategies.
• Analysis of late-stage functionalization techniques for DNA-encoded molecules.
• Critical assessment of reported synthetic protocols and their applicability.

Main Results:

• Identification of key metal-mediated reactions for DNA strand modification.
• Evaluation of the scope and limitations of current functionalization methods.
• Highlighting the potential for accessing novel chemical space through these pathways.

Conclusions:

• Metal-mediated synthesis provides powerful tools for DEL library construction.
• Late-stage functionalization enables exploration of diverse chemistries on DNA scaffolds.
• Understanding these methods is crucial for optimizing DEL-based drug discovery campaigns.