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Ruiz-Blanco, Y. B., Ponzo, I., Bravo-Rodriguez, K., Erkelenz, M., Schlücker, S., Uhlenbrock, G., Sanchez-Garcia, E., & Saccà, B. (2022). The role of DNA nanostructures in the catalytic properties of an allosterically regulated protease. Science Advances, 8(1), eabk0425. https://doi.org/10.1126/sciadv.abk0425 Download
Pacesa, M., Lin, C.-H., Cléry, A., Saha, A., Arantes, P. R., Bargsten, K., Irby, M. J., Allain, F. H.-T., Palermo, G., Cameron, P., Donohoue, P. D., & Jinek, M. (2022). Structural basis for Cas9 off-target activity. Cell, 185(22), 4067-4081.e21. https://doi.org/10.1016/j.cell.2022.09.026 Download
Tao, Y., Chen, L., Pan, M., Zhu, F., & Zhu, D. (2021). Tailored Biosensors for Drug Screening, Efficacy Assessment, and Toxicity Evaluation. ACS Sensors, 6(9), 3146–3162. https://doi.org/10.1021/acssensors.1c01600 Download
Kruse, M., Möser, C., Smith, D. M., Müller‐Landau, H., Rant, U., Hölzel, R., & Bier, F. F. (2022). Measuring Influenza A Virus and Peptide Interaction Using Electrically Controllable DNA Nanolevers. Advanced Materials Technologies, 7(5), 2101141. https://doi.org/10.1002/admt.202101141 Download
Xing, Y., Dorey, A., Jayasinghe, L., & Howorka, S. (2022). Highly shape- and size-tunable membrane nanopores made with DNA. Nature Nanotechnology, 17(7), 708–713. https://doi.org/10.1038/s41565-022-01116-1 Download
Figueiredo, F., Lopes-Marques, M., Almeida, B., Matscheko, N., Martins, P. M., Silva, A., & Macedo-Ribeiro, S. (2022). A Robust Assay to Monitor Ataxin-3 Amyloid Fibril Assembly. Cells, 11(12), 1969. https://doi.org/10.3390/cells11121969 Download
Kruse, M., Altattan, B., Laux, E.-M., Grasse, N., Heinig, L., Möser, C., Smith, D. M., & Hölzel, R. (2022). Characterization of binding interactions of SARS-CoV-2 spike protein and DNA-peptide nanostructures. Scientific Reports, 12(1), 12828. https://doi.org/10.1038/s41598-022-16914-9 Download
Schulte, C., Soldà, A., Spänig, S., Adams, N., Bekić, I., Streicher, W., Heider, D., Strasser, R., & Maric, H. M. (2022). Multivalent binding kinetics resolved by fluorescence proximity sensing. Communications Biology, 5(1), 1070. https://doi.org/10.1038/s42003-022-03997-3 Download
Ramotowska, S., Spisz, P., Brzeski, J., Ciesielska, A., & Makowski, M. (2022). Application of the SwitchSense Technique for the Study of Small Molecules’ (Ethidium Bromide and Selected Sulfonamide Derivatives) Affinity to DNA in Real Time. The Journal of Physical Chemistry B, 126(38), 7238–7251. https://doi.org/10.1021/acs.jpcb.2c03138 Download
Reinking, H. K., Kang, H.-S., Götz, M. J., Li, H.-Y., Kieser, A., Zhao, S., Acampora, A. C., Weickert, P., Fessler, E., Jae, L. T., Sattler, M., & Stingele, J. (2020). DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease. Molecular Cell, 80(1), 102-113.e6. https://doi.org/10.1016/j.molcel.2020.08.003 Download
Vicente, C. M., Girardet, J.-M., Hôtel, L., & Aigle, B. (2020). Molecular Dynamics to Elucidate the DNA-Binding Activity of AlpZ, a Member of the Gamma-Butyrolactone Receptor Family in Streptomyces ambofaciens. Frontiers in Microbiology, 11, 1255. https://doi.org/10.3389/fmicb.2020.01255 Download
Heerwig, A., Kick, A., Sommerfeld, P., Eimermacher, S., Hartung, F., Laube, M., Fischer, D., Pietzsch, H.-J., Pietzsch, J., Löser, R., Mertig, M., Pietsch, M., & Wodtke, R. (2023). The Impact of Nε-Acryloyllysine Piperazides on the Conformational Dynamics of Transglutaminase 2. International Journal of Molecular Sciences, 24(2), 1650. https://doi.org/10.3390/ijms24021650 Download
Mak, S., Marszal, A., Matscheko, N., & Rant, U. (2023). Kinetic analysis of ternary and binary binding modes of the bispecific antibody emicizumab. MAbs, 15(1), 2149053. https://doi.org/10.1080/19420862.2022.2149053 Download
Bchini, R., Girardet, J., Sormani, R., Gelhaye, E., & Morel‐Rouhier, M. (2021). Oxidized glutathione promotes association between eukaryotic translation elongation factor 1Bγ and Ure2p glutathione transferase from Phanerochaete chrysosporium. The FEBS Journal, 288(9), 2956–2969. https://doi.org/10.1111/febs.15614 Download
Wagenbauer, K. F., Pham, N., Gottschlich, A., Kick, B., Kozina, V., Frank, C., Trninic, D., Stömmer, P., Grünmeier, R., Carlini, E., Tsiverioti, C. A., Kobold, S., Funke, J. J., & Dietz, H. (2023). Programmable multispecific DNA-origami-based T-cell engagers. Nature Nanotechnology. https://doi.org/10.1038/s41565-023-01471-7 Download
Al-Amin, R. A., Muthelo, P. M., Abdurakhmanov, E., Vincke, C., Amin, S. P., Muyldermans, S., Danielson, U. H., & Landegren, U. (2022). Sensitive Protein Detection Using Site-Specifically Oligonucleotide-Conjugated Nanobodies. Analytical Chemistry, 94(28), 10054–10061. https://doi.org/10.1021/acs.analchem.2c00584 Download
Sijacki, T., Alcón, P., Chen, Z. A., McLaughlin, S. H., Shakeel, S., Rappsilber, J., & Passmore, L. A. (2022). The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination. Nature Structural & Molecular Biology, 29(9), 881–890. https://doi.org/10.1038/s41594-022-00820-9 Download
Ranallo, S., Bracaglia, S., Sorrentino, D., & Ricci, F. (2023). Synthetic Antigen-Conjugated DNA Systems for Antibody Detection and Characterization. ACS Sensors, 8(7), 2415–2426. https://doi.org/10.1021/acssensors.3c00564 Download