DELs Inside Cells.

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• DNA-encoded libraries (DELs) are powerful tools for identifying small molecules that bind to biological targets.
• Traditional DEL screening often occurs outside of the cellular environment, limiting the discovery of compounds targeting intracellular proteins in their native state.

Purpose of the Study:

• To describe a novel method for introducing DNA-encoded libraries into living cells.
• To demonstrate the feasibility of recovering DNA-molecule conjugates that bind to intracellular targets within a cellular context.

Main Methods:

• Development of a method to deliver DNA-encoded libraries into living cells.
• Isolation and sequencing of DNA tags from conjugates that bound to intracellular targets.
• Proof-of-principle validation of the approach using model intracellular targets.

Main Results:

• Successful introduction of DNA-encoded libraries into living cells.
• Recovery of specific DNA-molecule conjugates that demonstrated binding to intracellular targets.
• Demonstration that DELs can be screened against native intracellular protein targets.

Conclusions:

• The developed method enables the screening of DNA-encoded libraries within the complex environment of living cells.
• This approach facilitates the discovery of novel small molecules that interact with intracellular targets in their native physiological state.
• The findings suggest a promising new strategy for drug discovery and chemical biology research.