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]

What We Do for DELs

At Alfa Chemistry, we use the latest synthetic chemistry technology and automated synthesis platform to construct the expected DELs, and provide one-stop service for DEL synthesis and DEL screening.

• 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. Based on tens of thousands of high-quality molecular building blocks with diverse structures, Alfa Chemistry has the excellent ability to construct DELs with diverse chemical spaces, novel structures, and billions of compounds.

• 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.

Choose Alfa Chemistry

With our unparalleled expertise and commitment to quality, Alfa Chemistry is poised to help drive the next wave of innovation in drug discovery through our DEL construction and synthesis services. To get started with our services, or to discuss our capabilities with a member of our expert team, contact us today.

References

• Adrián Gironda-Martínez, et al. ACS Pharmacol. Transl. Sci., 2021, 4, 4, 1265-1279.
• Nicholas Favalli, et al. FEBS Lett., 2018, 592, 2168-2180.