Binding Kinetics I Conformational Changes
|Affinity, dose response||KD, IC50, fM sensitivity||Protein diameter||DH, ΔDH = 0.1 nm|
|Kinetics||kON, kOFF||Thermodynamics||ΔH, ΔS, ΔG|
|Avidity, bispecifics||Two-color detection||Nucleic acid enzyme activity||kCAT, KM, kEXO|
|Conformational changes||% friction change|
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Dr. Michael Schraeml, Head Protein and Enzyme Technologies
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Browse through the latest publications.
Paper in Nature Communications I 18 June 2021
The paper shows that an engineered anti-Her2 tetravalent antibody construct that binds to two different Her2 epitopes (biparatopic) significantly increases the anti-tumoral efficacy over trastuzumab or pertuzumab treatments. The biparatopic tetravalent antibody induces cluster formation of Her2 molecules on the cancer cell surface by its crosslinking capabilities leading to enhanced Her2 growth factor receptor internalization and degradation.
Besides determination of precise binding kinetics of all constructs, the superior distance-dependent crosslinking capabilities of the tetravalent construct over its parental antibody constructs at different Her2 surface densities were measured and quantified by the switchSENSE® technology. A dynamicBIOSENSORS’ internal simulation algorithm confirmed the measured crosslinking effects at different Her2 densities.
Paper in PNAS I 30 March 2021
CMT2N-causing aminoacylation domain mutants enable Nrp1 interaction with AlaRS
Our collaborators at Scripps Research Institute used the switchSENSE® technology in this paper to analyze the different conformations of the wild-type and mutant versions of the alanyl-tRNA synthetase protein (AlaRS).
The switchSENSE® conformation analysis robustly detected four mutations in AlaRS leading to up to 12% size increase over the wild-type as major drivers of tRNA synthetase expansion. These results were confirmed by further independent biophysical analyses (small-angle X-ray scattering and hydrogendeuterium exchange). Interestingly, an expansion of the protein by mutations in the aminoacylation domain was shown to correlate with increased neuropilin 1 (Nrp 1) binding capabilities and disease severity of the Charcot-Marie-Tooth disease, a neurological disorder.
With this finding, the conformation analysis helped to understand the connection between AlaRS expansion and Nrp binding, thus providing more insights to potentially cure this inherited disorder.
Paper in Environmental Toxicology and Pharmacology I November 2020
Chlordecone (CLD) is a chlorinated persistent organic pollutant (POP) whose presence despite the 1993 ban in agriculture areas has caused numerous public health concerns. CLD accumulates in the liver, and the CLD metabolite, chlordecol (CLD-OH) is found in bile, an important site of excretion for cholesterol transported to the liver via lipoproteins.
Here, we studied the real-time molecular interaction between CLD and CLD-OH with human serum lipoproteins, LDL and HDL. While no interaction was detected between CLD and HDL, or between CLD-OH and LDL, relatively high specific affinities were observed between CLD and CLD-OH for LDL and HDL, respectively.