Development of a virus biosensor platform based on multivalent synthetic nanoswitches
Biological and Biomimetic Chemistry
Final Report Abstract
The aim of the proposed project was the development of a biosensing platform based on autoinhibited nanoswitches for fast and sensitive detection of complex viral structures. The initial nanoswitch design could detect hemagglutinin, the major surface protein of Influenza A, however, only with low sensitivity and robustness. Therefore, the design of the nanoswitches and their components was optimized, yielding molecular biosensors with high sensitivity and modularity. Multiple key aspects were crucial to arrive at the optimized design; 1) Screening and identification of suitable peptide linkers in the protein switches, 2) Well characterized, genetically encoded complementation inhibitors for the signal actuator, and 3) initial separation of the parts that bind the target molecule and the part that reports on the binding event. The successful strategy to screen peptide linkers and the characterization of suitable complementation inhibitors were published in journals of the American Chemical Society (ACS). The development of the virus sensing platform continues in the scope of a EuroTechPostdoc fellowship. In the future, the scientific results will allow to develop potent biosensors for virus diagnostics at the point of care and thus prevent virus spreading within a population.
Publications
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Bioluminescence Goes Dark: Boosting the Performance of Bioluminescent Sensor Proteins Using Complementation Inhibitors. ACS Sensors, 7(12), 3800-3808.
Gräwe, Alexander & Merkx, Maarten
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iFLinkC-X: A Scalable Framework to Assemble Bespoke Genetically Encoded Co-polymeric Linkers of Variable Lengths and Amino Acid Composition. Bioconjugate Chemistry, 33(7), 1415-1421.
Gräwe, Alexander; Merkx, Maarten & Stein, Viktor
