Binding Kinetics I Conformational Changes
DISCOVER MOLECULAR INTERACTIONS using switchSENSE® – comprehensive biophysical information,
in one measurement.
Every day, scientists all over the world strive to unravel the secrets of life. How do diseases develop? How can we treat them? In order to answer these big questions, we need to start small. We need to understand the tiny building blocks: molecules. How big are they? What is their structure? How do they interact with each other? The answers to these questions will guide us towards new and improved medicines to treat diseases like cancer.
At Dynamic Biosensors, we have made it our mission to support scientists in this endeavor and to help accelerate the drug discovery process. To fulfil this, we developed switchSENSE® – a groundbreaking technology that enables researchers to characterize molecular interactions in unequaled detail.
RESEARCH TECHNOLOGY ADVANCES
made for high-performance analysis.
Coupling & capture kits, starter packs, tutorial & test kits, buffers, solutions and other consumables.
Dr. Michael Schraeml, Head Protein and Enzyme Technologies
ROCHE DIAGNOSTICS GMBH
Browse through the latest publications.
Paper in Nature Portfolio I 27 July 2022
Congratulations to Marlen Kruse and all collaborators from Ralph Hölzel’s group at Fraunhofer Institute to their interesting publication in Scientific Reports.
They investigated the interaction between the SARS-CoV-2 spike protein and its receptor hACE2. To do so, they prepared trivalent DNA-peptide nanostructures to achieve a trimeric hACE2 peptide presentation. switchSENSE® was used to examine the binding of full-length spike protein, subdomains and even whole virus particles. They show that small changes in the amino acid sequence of the spike protein can drastically influence the binding behavior. Furthermore, they demonstrate an increased affinity of the protein to the trivalent peptide construct as compared to single peptides. Finally, they detect different binding behaviors of several pseudo virus models of the Alpha and Beta variants of SARS-CoV-2 compared to the inactivated wild type virus.
This study shows the versatility of the switchSENSE® technology, which enables the investigation of multivalent interactions and the utilization of a broad range of analytes from protein subdomains to whole virus particles.
Paper in MDPI I 19 June 2022
In this paper, Francisco Figueiredo and our collaborators from Sandra Macedo-Ribeiro‘s group demonstrate how the switchSENSE® technology can be used to investigate aberrant protein self-assembly in neurodegenerative diseases.
They are investigating the aggregation of a protein called Ataxin-3. Ataxin-3 mutations can cause the expansion of a polyglutamine stretch within the protein. These mutated forms of Ataxin-3 can self-assemble into oligomeric amyloid structures and cause the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3). They developed an assay to monitor the aggregation of wild type and mutated Ataxin-3 and used it to investigate the impact of different conditions (e.g. pH, detergents, etc) on the aggregation. With the help of the switchSENSE® technology they quantified the kinetics of the aggregation-prone domain as well as the full length wild type protein.
Paper in Nature Portfolio (under review) I 28 April 2022
They investigated peptide-based effectors inhibiting protein-protein interactions (PPI) and demonstrated the value of switchSENSE® to analyse structure-activity relationships. They synthesized >100 unique multivalent peptide binders and used switchSENSE® to systematically evaluate their binding kinetics.
In this paper they show that specific peptide architectures influence the binding dynamics, which enabled them to identify highly inhibitory peptides. The binding affinity was increased for higher-order multimers, which was mainly driven by increased on-rates. Precise on- and off-rate determination is thus key to engineer optimized multivalent binders.
switchSENSE® was demonstrated to be a viable method for high-throughput PPI characterization in order to optimize peptide architectures and engineer most efficient multivalent effectors. More specifically, switchSENSE® showed superior accuracy and low sample consumption when compared to alternative biophysical methods.
Paper in Nature Nanotechnology I 28 April 2022
Congratulations to Yongzheng Xing and our collaborators from Stefan Howorka’s lab for their notable publication in Nature Nanotechnology!
They designed synthetic nanopores using molecular design with DNA. Nanopores can be used to perform single-molecule analyses by measuring changes in current as individual molecules block the pore. Their nanopore design consists of bundles of DNA duplexes which form subunits and can be arranged in a modular way to create versatile polygonal shapes and sizes that do not exist in nature.
They confirmed the applicability of their pores as sensors by detecting single molecules of anti-biotin antibodies within pores modified with biotin tags. They further attached SARS-CoV-2 spike proteins into the pore lumen and demonstrated the usage as a sensor for SARS-CoV-2 antibodies. Due to its high validity, the switchSENSE® technology was used to verify the kinetic data of the biotin antibody binding experiment.
Paper in Science Advances I 05 Jan 2022
Congratulations to Richard Kosinski and our collaborators from Barbara Saccà’s group at the University of Duisburg-Essen for this outstanding Science Advances paper.
This work addresses key questions on kinetic properties of DNA-scaffolded enzymes using thrombin, a model of allosterically regulated serine proteases, encaged into DNA origami cavities with distinct structural and electrostatic features.
Besides demonstrating how DNA nanostructures affect charge-dependent mechanisms of encaged enzymes, thereby offering an alternative strategy to regulate allosteric processes through spatial confinement, the kinetic binding properties of thrombin were also characterized with switchSENSE® technology. The switchSENSE® biosensor is ideal to study DNA-protein interaction, and it was used to support the findings on the thrombin binding properties to the thrombin-binding DNA aptamers.
Press Release I 01 September 2022
Munich, Germany, and Regensburg, Germany, 01 September 2022 – Dynamic Biosensors and 2bind, a Contract Research Organization (CRO), today announce that they have signed a technology-service partnership which will enable both companies to further help their customers to accelerate research. The collaboration will enable 2bind to integrate Dynamic Biosensors’ innovative heliX® system into its service portfolio, giving Dynamic Biosensors another highly experienced partner in the areas of certified services and beta-testing of future technologies.
2bind is a highly respected CRO focused on early-stage drug discovery and antibody development, with more than 10 years’ market experience. Its customers will benefit from innovative biophysical binding assays based on Dynamic Biosensor’s proprietary switchSENSE® technology, which leverages DNA nanolevers to determine the size and shape of biomolecules.
Thomas Schubert, CEO of 2bind, commented: “2bind has built up a unique portfolio of biophysical methods and assays to offer customized outsourcing solutions in early drug discovery and antibody development. By integrating Dynamic Biosensors’ cutting-edge heliX® biosensor system, we are gaining another powerful tool to meet our customers’ needs and enhance their research capabilities. The innovative switchSENSE® technology features one of the broadest application ranges of any bioanalytical tool. In addition to direct kinetic binding analysis, it provides detection of avidity / cooperative binding and formation of ternary complexes, which are especially useful for programs involving bi-specific antibodies or PROTAC/molecular glue compounds. The heliX® biosensor also enables the monitoring of conformational changes in proteins, induced for example upon ligand binding. These versatile analysis modes will enrich 2bind’s hit validation capabilities in small molecule and antibody discovery programs. 2bind is proud to become a certified service provider for Dynamic Biosensors’ innovative products and we look forward to driving scientific advances through our expertise in biophysics.”
The partnership positions 2bind as a trusted service partner for the switchSENSE® technology and as a development site for beta-testing novel developments aimed at strengthening Dynamic Biosensors’ product portfolio with cutting-edge tools for biomolecular interaction analysis.
Ralf Strasser, COO of Dynamic Biosensors, said: “2bind and Dynamic Biosensors share a strong commitment to helping our customers achieve scientific breakthroughs. This agreement underlines the importance of early drug discovery for our business. The high-quality information offered by switchSENSE® also helps lower the attrition rate for drug candidates in later, more expensive stages of drug development. Partnering with 2bind supports our mission to bring innovative methodologies to the market and to drive the expansion of the heliX® biosensor system by demonstrating its benefits to researchers around the world.”
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About Dynamic Biosensors
Dynamic Biosensors is a provider of instruments, consumables, and services in the field of analytical systems for the characterization of biomolecules and molecular interactions. The company commercializes switchSENSE® technology, a groundbreaking platform technology for the analysis of biomolecules with applications in R&D and drug development. The switchSENSE® technology is protected worldwide and only available through Dynamic Biosensors. The company is headquartered in Munich, Germany – a vital center of Europe´s biotechnology industry – and has offices in the United States, the United Kingdom, France, Japan and Singapore. www.dynamic-biosensors.com
2bind is a provider of biophysical analytical services with a focus on drug discovery and antibody development, headquartered in Regensburg, Germany. 2bind´s mission is to accelerate customer research by developing and preforming high-end, scalable, and cost-efficient assays based on innovative biophysical technologies. 2bind´s customers benefit from expert knowledge in biophysics and the experience of >1000 projects with >350 customers. www.2bind.com
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