1. Screening Libraries
  2. DNA-Encoded Compound Library: Synthesis and Screening

DNA-Encoded Compound Library: Synthesis and Screening

DNA Encoded compound Library (DEL) technology has emerged as an enabling tool in the drug discovery field, featured with an incredibly convenient and rapid way to assess the binding affinity of billions of chemical compounds and discover potential ligands for biological and pharmaceutical interested protein targets. DEL synthesis starts with an oligonucleotide that contains a chemical linker moiety, and proceeds through iterative cycles of DNA barcode elongation and chemical synthesis. Comparing with conventional high-throughput screening (HTS), DEL screening requires little protein, minimal assay development and no specialized instrumentation. Through next-generation sequencing and data analysis, it’s easy for hit identification by sequencing the DNA barcode associated with building block.

Figure 1. Overview of DNA-Encoded Library (DEL) Technology. (A) DEL synthesis. (B) DEL screening.

DEL construction and synthesis

DNA-encoded libraries are built with combinatorial chemistry, which works by bringing building blocks together to generate unique structures. The acquisition of building blocks is a large impediment when setting up a successful DEL platform. Based on more than 50,000 high-quality building blocks, MCE eliminates "bad" chemical structures such as DNA intercalators, building blocks containing N-halogens, heavy metals, and retains compounds with unique skeletons, novel structures, diverse functional groups and abundant chemical spaces. Combining with hundreds of DNA compatible reactions, MCE synthesized a series of DNA-encoded libraries consisting of billions of compounds with abundant chemical spaces and novel structures.

Figure 2. DEL construction.

DEL libraries

3 Kits:

  • DEL A Kit:

    20 DEL libraries, covering over 300 million DEL molecules, 1 tube set
  • DEL B Kit:

    50 DEL libraries, covering over 1 billion DEL molecules, 1 tube set
  • DEL A+B Kit:

    A+B combination

2 Package Sizes:

  • 5 nmol、20 nmol

Key Features of DEL libraries

  • 68 DEL libraries, covering over 1.3 billion DEL molecules.
  • Abundant chemical spaces, novel structures, lead-like and drug-like molecular properties.
  • Powerful synthesis ability.
  • Strict quality control and verification system.
  • Automated product and data management system.

DNA Encoded compound Library screening

DEL selections require little protein, minimal assay development and no specialized instrumentation. Following DEL synthesis, the assembled compounds are incubated with the biomolecular target affixed to a solid support (polymer or resin). Low affinity ligands are washed away, after which the DNA barcode of the remaining high affinity ligands can be PCR-amplified for hit identification by sequencing the DNA barcode associated with each small molecule building block.

Figure 3. Affinity-based DEL selections against an immobilized target protein.

DEL Screening Processes

  • a.The target protein (blue), immobillized on solid support, is incubated with the DNA-encoded library (DEL).
  • b.Unbound library members are washed away by means of consecutive washing steps.
  • c.Library members bound to the target protein are eluted.
  • d.After final elution, the DNA tags on the eluted protein-binding library members are amplified by PCR.
  • e.The amplified DNA tags are subjected to next-generation DNA sequencing, and the resulting data can be plotted to visualize the final barcode counts for each DECL member.

Key Features of DEL Screening

  • One-stop service: DEL synthesis and screening.
  • Small amount of protein sample: protein (depending on the molecular weight of the protein).
  • Short turn-around time: 4-5 weeks.
  • Professional R&D team of DEL technology.
  • Stringent QC standards with competitive prices.