Drugging the “undruggables”: PROTACs, dimerization, and more
Overcome the challenge of analyzing small-molecules, which inhibit or stabilize
protein-protein interactions (PPIs). Introducing the DNA Y-structure.
Analysis of ternary binding
by induced proximity with
the DNA Y-structure
Using switchSENSE® technology and the novel DNA Y-structure, we can characterize ternary complex formation of bifunctional small molecules like PROTACs and molecular glues.
The target proteins can be functionalized on the end of the two FRET pair color-coded Y-arms of the structure. The Y-structure closes upon small molecule binding, and the subsequent ternary complex formation brings together the green donor and the red acceptor dye into a closer, FRET sensitive, distance. The change in red fluorescence signal intensity directly correlates with ternary complex formation kinetics.
With the heliX® biosensor and its highly sensitive FRET read-out, it is possible to perform high-throughput screening and ranking of bifunctional small molecules.
Thanks to its unique supramolecular DNA biochip design, switchSENSE® is ideal for the analysis of ternary complex formation vs binary interactions in the context of PROTAC/molecular glues and protein degradation.
Create Homo- or Hetero-protein immobilization on the biosensor surface.
Hit screening of compounds that interfere in PPIs.
Low sample consumption.
Use FRET or standard fluorescence change to measure the interaction.
Highly sensitive for detecting weak and tight binders.
“At Merck, we see the switchSENSE® technology as a versatile and highly valuable tool to positively impact preclinical drug discovery projects. switchSENSE® has proven to be extremely helpful when it comes to the analysis of interactions between a drug candidate and its target protein.
Especially the formation of ternary complexes (DNA-Enzyme-Drug) and being able to detect the inhibition of the enzymatic activity is a big benefit. Moreover, we highly appreciate the support and the competence of the dynamicBIOSENSORS team.”
“switchSENSE® was a revelation: it solved a seemingly intractable antibody/antigen measurement with ease. The key was its remarkably versatile architecture, switchSENSE® seems only limited by the imagination of the researcher.“
“The architectures available from switchSENSE® are uniquely placed to offer us the flexibility and extraordinary sensitivity in our molecular interaction studies. This new technology will immediately open up a number of new research approaches, previously unattainable from existing technologies.“
→ Read more about what our customers say about us.
Find exemplary applications in life science research and drug discovery, for which switchSENSE® provides unique capabilites. Browse through publications, application notes, tutorials, and more.
Measure the kinetics and affinities of DNA/RNA binding proteins directly with switchSENSE®’s unique DNA nanolever approach.
Unravel the behaviour of complex binders like antibodies, PROTACs, and other ternary complexes with switchSENSE®’s versatile binding assays.
Conformation & Size
Solve the structure=function equation and study conformational changes in real-time with switchSENSE®’s dynamic measurement mode.
Discuss your specific needs with our specialists.