Target Deconvolution for Early-Phase Drug Discovery

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Promega and MS Bioworks provide expertise in chemistry, target isolation and proteomics to help accelerate the target deconvolution process. The service is based on a new live-cell target identification method that overcomes key challenges of other live-cell and lysate-based approaches.

MS Bioworks

How the Service Works

You provide the target compound.

Target compound
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The target compound is modified to include a chloroalkane ligand.

Chloroalkane ligand binds irreversibly and specifically to HaloTag® Protein.

Chloroalkane ligand binds to target compound
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Control experiments verify the modified compound:

  • Produces the desired phenotype in a cell-based assay
  • Is cell-permeable
  • Binds to the HaloTag® Protein
Control experiments verify modified compound
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Proteins that interact with the compound are captured in pull-down assays.

Cells are treated with modified compound or no-compound control

Cells are treated with the modified compound or a no-compound control

Cells are lysed and interacting proteins captured

Cells are lysed and interacting proteins captured using HaloTag® Resin

Interacting proteins are eluted using parentlal compound

Interacting proteins are eluted using parental compound

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Interacting partners are identified by mass spectrometry.

Proteins are digested and identified

Proteins are digested and identified

You receive a comprehensive report

You receive a full report of enriched proteins that interact with the small molecule in your cell line of interest

Premier Protein Capture Technology Enables Rapid Capture of Interacting Proteins from Live Cells

Precise identification of proteins that interact with target compounds is made possible using HaloTag® technology—a comprehensive platform for functional protein analysis.

  • Potency and permeability of tagged small molecules remains unchanged. Interacting targets are captured using a novel chloroalkane tag, which has minimal effect on compound potency and permeability.
  • Protein targets are captured in live cells, ensuring relevancy of results. Modified compounds engage with their targets inside cells, so interactions occur under conditions relevant to the desired cellular phenotype.
  • Enrichment method allows capture of low-abundance and low-affinity targets. Enrichment of interacting targets is achieved through efficient capture of the chloroalkane-tagged compound onto immobilized HaloTag® Protein. The rapid and selective nature of the process facilitates identification of low-affinity or low-abundance targets.
Deciphering the cellular targets of bioactive compounds using a chloroalkane capture tag

Read more about the technology in the paper Deciphering the cellular targets of bioactive compounds using a chloroalkane capture tag. Ohana, R.F., et al. (2015) ACS Chem Biol. 10(10), 2316-24.

Collaborative and Customizable

The service is customizable to your needs. You get access to the protein purification expertise of Promega scientists and the expert mass spec services of MS Bioworks, freeing up your team to concentrate on target optimization. Our stepwise analysis process uses your target compounds and your cell lines, and can be adjusted at any time.

The mass spectrometry expertise of MS Bioworks is applied to analyze and identify the HaloTag®-captured proteins. Through this service you get the people who know most about mass spec working for you. You get the data, and are free to proceed with optimization.