DNA-Encoded Chemical Library

What Is DEL Technology?

DELs (DNA-encoded chemical libraries) are collections of small molecules that are synthetically produced and chemically modified to attach to DNA segments. DNA acts as a code to track and identify individual molecules in the library. By encoding a single molecule with DNA, hundreds of millions of unique compounds can be stored in a library, allowing high-throughput screening of potential drug molecules for drug discovery and development. This technology rapidly speeds up the drug discovery process by enabling large-scale screening of different compounds.

An overview of DNA-encoded chemical libraries. [1]

• Construction And Synthesis of DELs

The construction of DELs involves the synthesis of large numbers of individual compounds, each of which is then linked to a unique DNA identifier.

• Single-pharmacophore DNA-encoded chemical libraries: Single-pharmacophore libraries are most commonly constructed using the DNA-recorded synthesis, which relies on the use of split-and-merge procedures.
• Dual-pharmacophore DNA-encoded chemical library: Dual-pharmacophore libraries are usually constructed using a coding strategy based on the self-assembly of partially complementary DNA strands.

Schematic representation of DNA-encoded chemical libraries. [2]

• Screening of DELs

Compared to conventional HTS, DEL technology offers the possibility to screen billions of molecules in a single experiment. Available screening methods include solid-phase affinity-based screening (such as magnetic beads and resin-filled tips), interaction-dependent PCR, and DNA photoaffinity labeling (DPAL).

DEL solid phase screening process:

• Protein immobilization and incubation: pre-immobilize the target protein to be screened, and then incubate the immobilized protein with the DEL library.
• Washing: Wash away DEL molecules that do not bind to proteins or have weak binding forces.
• Elution: The DEL molecules bound to the protein are eluted to achieve the enrichment of small molecules with high affinity.
• PCR amplification of DNA tags with protein-bound DEL molecules.
• High-throughput sequencing and data analysis: Perform next-generation sequencing on the amplified DNA tags, and decode compound information based on the DNA tags of DEL small molecules.