- Computer-Aided Drug Design (CADD)
- DNA-Encoded Library Technology (DELT)
- Fragment-Based Screening
- High Content Screening (HCS)
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High Throughput Screening (HTS)
- Automated HTS Platform
- Biochemical assays in Hit Characterization
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Biophysical Assays in Hit Characterization
- BLI for Affinity-based Hit Screening
- CD Spectrometry for Protein Structure Determination
- ITC for Binding Assessment
- MS for Structure Confirmation
- MT for Binding Affinity Measurement
- NMR Spectrometry for Tareget identification and Characterization
- SPR Spectrometrys for Structure Determination
- TSA for Protein's Stability Evaluation
- Cellular assays in Hit Characterization
- Drug Repurposing
- Hit Screening
- HTS Assay Development
- HTS Compounds Libraries
- HTS Data Management
- Virtual Screening (VS)
One-stop
Drug Discovery Services
- Experienced and qualified scientists functioning as project managers or study director
- Independent quality unit assuring regulatory compliance
- Methods validated per ICH GLP/GMP guidelines
- Rigorous sample tracking and handling procedures to prevent mistakes
- Controlled laboratory environment to prevent a whole new level of success
DNA-Encoded Library Screening
INQUIRYDNA encoded library screening, which is also known as DEL selection, is an affinity selection process. General DEL selection procedures involve library incubation and unbound molecule removal. In DEL screening, DEL technology can select a great number of bioactive small molecules and allows the efficient screening of unprecedented chemical diversity in a single vial.
Fig.1 Schematic of DNA-encoded library screening. (Yuen, L. H.; Franzini, R. M. 2016)Advantages of DEL Screening
- Have easy accesses to trillions of compounds.
- Reduce the consumption of protein.
- Rapid hit identification and validation.
- Cost effective.
Principle and Strategies of DEL Screening
DEL selection method is not only applied to find binders but also distinguish compounds with desired function. In DEL screening, very high concentration of targets (μM range) is required to to drive the equilibrium towards the formation of target-compound complexes. Therefore much lower compound concentration is needed (105 per compound or even lower) and trillions of compounds can be evaluated in a single vial.
Our DEL Selection Process
Pre-slection studies
We perform a careful assessment regarding the target activity confirmation and selection feasibility to ensure the success of DEL selection success.
DEL pooling
Hundreds of libraries are pooled to one or several DEL packages for target DEL selection and our scientists take target usage efficiency, target type, DEL type, optimal DEL population as well as DEL solubility into consideration.
Incubation
The immobilized target protein is incubated with a pooled DEL in which proteins and compounds are incubated in solution before capturing the complex on solid support.
Washing
We then conduct the washing operation to remove weak binders with buffers whereas molecules with high target affinity are retained on the solid support.
Release of binders
The molecules of the DNA-encoded library enriched with binders are then eluted by heat denaturation of the target protein.
Additional Services of DEL Screening
DEL selection processes for different DEL types
We provide various DEL selection options including different types of libraries, copy number in each sample, etc., to achieve high data usage efficiency.
DEL selection compound input
DEL input refers to the copy number of individual DEL molecule in the selection. We have a systematic investigation on the relationship between DEL input and selection performance.
DEL Selection Target Requirements
- >90% purity.
- Compatible wit His, biotin, Strep, GST, FLAG and Fc tags.
- Tag is not allowed to impair target activity and functionality.
- The amount of required protein is based on the selection group design.
Our Capabilities of DEL Screening Services
- We perform a thorough assessment of each component such as selection conditions and immobilization, to ensure that target shows good activity.
- Our groups offer efficient and flexible DEL pooling strategies with assistance of automatic or semi-automatic instrumentation. Furthermore, we also provide customized pooling projects to meet specific requirement.
- We can also perform manual or automatic washing process to deplete any non-binding compounds to achieve rapid screening of dozens of proteins.
- At BOC Sciences, we perform two or three rounds of selection to increase the stringency of the selection process.
Reference
- Yuen, L. H.; Franzini, R. M. Achievements, Challenges, and Opportunities in DNA‐Encoded Library Research: An Academic Point of View. Chembiochem A European Journal of Chemical Biology, 2016, 18(9): 829.
※ It should be noted that our service is only used for research.
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