Discover protein-protein interaction inhibitors with our unique drug discovery technology
– partner with Vipergen
DELs in Cells – PPI Inhibitor Direct
DELs in Cells – PPI Inhibitor Direct enables direct discovery of PPI inhibitors for your target protein
DELs in Cells – PPI Inhibitor Direct in brief:
You provide:
The amino acid sequences of each of the target proteins of interest (POI).We do:
Expression and DEL screening of the POIs in a living cell.
DEL screening is performed in two formats:
• Individual expression of POIs (monoplex) to discover compounds binding to each POI.
• Co-expressed POIs (duplex) to distinguish PPI inhibitor hits from plain POI binders.You receive:
A hit list and a report to advance your drug discovery project.Timelines:
Expression study: Typically one month
DEL Screening: Typically one month
DELs in Cells – PPI Inhibitor Direct provides an excellent choice for targets, where disruption of protein-protein interaction is the preferred pharmaceutical mode of action.
DELs in Cells – PPI inhibitor Direct. Discover PPI inhibitors in living cells.
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Streamlined discovery of PPI inhibitors
DELs in Cells – PPI Inhibitor Direct projects are conducted in two distinct phases:
Feasibility study to enable balanced expression of the POIs
- Design of constructs for expression
- Co-expression of the POIs in Xenopus oocytes
- Evaluation of expression by Western blotting
There is no requirement for purified target proteins – the POIs are expressed as an intrinsic part of the project.
Our scientists have a strong history of successfully expressing target proteins in Xenopus oocytes, with over 95% of projects succeeding at this stage.
DEL screening in monoplex and duplex configurations
- Balanced expression of POIs in Xenopus oocytes
- DEL and Bait-DNAs are injected into the cell
- Binding is encoded via ligation in emulsion
- Hits are identified by DNA sequencing and decoding
After identification of the hits through DNA sequencing and decoding, they are grouped into clusters based on structural similarity and reported to the partner. The duplex cBTE screening technology facilitates the differential mapping of PPI inhibitor hits from other POI binding compounds.
How is direct screening for PPI inhibitors enabled?
Our team of molecular biologists and chemists are experts in screening technologies and have a strong track record of delivering fast and reliable results.
We have optimized DEL screening in living cells to enable direct screening for PPI inhibitors.
Expression and screening in Xenopus oocytes
With DELs in Cells – PPI Inhibitor Direct, you only need to provide the amino acid sequences of the POIs. Protein expression is an intrinsic part of the process, eliminating the need for purified target proteins.
Screening in a duplex setup
Due to the multiplexing capability of the cBTE screening technology, compounds inhibiting the formation of the POI1-POI2 complex can be distinguished from compounds that are just binding the POIs.
Data analysis
The screening results are analyzed to identify hits and map their binding interactions. Concurrently, nonspecific binders are excluded, leaving a refined dataset that includes only high-quality hits in the final report.
DELs in Cells based screening for protein-protein interaction inhibitors
The cellular Binder Trap Enrichment (cBTE) technology was invented to enable DEL screening in a living cell.
For direct discovery of PPI inhibitors, cBTE screening is employed in a unique duplexed format.
The multiplexing capability allows for the simultaneous screening of multiple POIs in a single living cell. This is achieved by tagging each POI with barcoded Bait-DNA. The Bait-DNA barcodes are subsequently used to map POI1, POI2, and the complex between them, respectively, as binders for the DEL hits.
For a DELs in Cells – PPI Inhibitor Direct screening program, the POIs are screened in both monoplex and duplex formats, enabling the characterization of binding events, and thereby facilitating direct identification of PPI inhibitors:
- Discovery of compounds able to bind POI1 or POI2, respectively (Monoplex experiment)
- Distinction of PPI inhibitor compounds from plain POI binders (Duplex experiment, taking advantage of the POI1 and POI2 barcoding)
Frequently Asked Questions
Is purified protein necessary to initiate DEL screening in cells?
No, unlike other screening technologies, only the amino acid sequence of the target protein is needed to execute the screening project, enabling a rapid progression from project initiation to hits that provides our partners with a competitive edge.
How is the expression of the target proteins in the cell validated?
The target protein expression is ensured by Western blotting, a rapid technology enabling semi-quantitative and qualitative assessment of the expressed protein’s integrity.
Which target classes can be screened in cells?
The screening of most cytoplasmic proteins, including membrane proteins accessible from the cytoplasm, can be conducted in cells. Various protein classes, encompassing enzymes, protein-protein interaction targets, molecular glue targets, and many more have been screened in this format.
How is diversity and novelty ensured in the DNA encoded libraries?
Diversity and novelty are assured by the diversity of the building blocks incorporated into the design of our libraries. A substantial portion of the building blocks, used in library synthesis, is designed in-house. This approach ensures the novelty of the resulting compounds in the library.