{"language":[{"iso":"eng"}],"publication":"International Journal of Molecular Sciences","user_id":"67287","year":"2023","status":"public","_id":"50150","type":"journal_article","keyword":["Inorganic Chemistry","Organic Chemistry","Physical and Theoretical Chemistry","Computer Science Applications","Spectroscopy","Molecular Biology","General Medicine","Catalysis"],"publisher":"MDPI AG","article_number":"7226","citation":{"short":"P. Müller, M. Meta, J.L. Meidner, M. Schwickert, J. Meyr, K. Schwickert, C. Kersten, C. Zimmer, S.J. Hammerschmidt, A. Frey, A. Lahu, S. de la Hoz-Rodríguez, L. Agost-Beltrán, S. Rodríguez, K. Diemer, W. Neumann, F.V. Gonzàlez, B. Engels, T. Schirmeister, International Journal of Molecular Sciences 24 (2023).","ama":"Müller P, Meta M, Meidner JL, et al. Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study. <i>International Journal of Molecular Sciences</i>. 2023;24(8). doi:<a href=\"https://doi.org/10.3390/ijms24087226\">10.3390/ijms24087226</a>","ieee":"P. Müller <i>et al.</i>, “Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study,” <i>International Journal of Molecular Sciences</i>, vol. 24, no. 8, Art. no. 7226, 2023, doi: <a href=\"https://doi.org/10.3390/ijms24087226\">10.3390/ijms24087226</a>.","bibtex":"@article{Müller_Meta_Meidner_Schwickert_Meyr_Schwickert_Kersten_Zimmer_Hammerschmidt_Frey_et al._2023, title={Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study}, volume={24}, DOI={<a href=\"https://doi.org/10.3390/ijms24087226\">10.3390/ijms24087226</a>}, number={87226}, journal={International Journal of Molecular Sciences}, publisher={MDPI AG}, author={Müller, Patrick and Meta, Mergim and Meidner, Jan Laurenz and Schwickert, Marvin and Meyr, Jessica and Schwickert, Kevin and Kersten, Christian and Zimmer, Collin and Hammerschmidt, Stefan Josef and Frey, Ariane and et al.}, year={2023} }","chicago":"Müller, Patrick, Mergim Meta, Jan Laurenz Meidner, Marvin Schwickert, Jessica Meyr, Kevin Schwickert, Christian Kersten, et al. “Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study.” <i>International Journal of Molecular Sciences</i> 24, no. 8 (2023). <a href=\"https://doi.org/10.3390/ijms24087226\">https://doi.org/10.3390/ijms24087226</a>.","mla":"Müller, Patrick, et al. “Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study.” <i>International Journal of Molecular Sciences</i>, vol. 24, no. 8, 7226, MDPI AG, 2023, doi:<a href=\"https://doi.org/10.3390/ijms24087226\">10.3390/ijms24087226</a>.","apa":"Müller, P., Meta, M., Meidner, J. L., Schwickert, M., Meyr, J., Schwickert, K., Kersten, C., Zimmer, C., Hammerschmidt, S. J., Frey, A., Lahu, A., de la Hoz-Rodríguez, S., Agost-Beltrán, L., Rodríguez, S., Diemer, K., Neumann, W., Gonzàlez, F. V., Engels, B., &#38; Schirmeister, T. (2023). Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study. <i>International Journal of Molecular Sciences</i>, <i>24</i>(8), Article 7226. <a href=\"https://doi.org/10.3390/ijms24087226\">https://doi.org/10.3390/ijms24087226</a>"},"date_updated":"2024-01-05T12:59:32Z","issue":"8","intvolume":"        24","abstract":[{"lang":"eng","text":"<jats:p>Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.</jats:p>"}],"title":"Investigation of the Compatibility between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study","publication_identifier":{"issn":["1422-0067"]},"author":[{"full_name":"Müller, Patrick","last_name":"Müller","first_name":"Patrick"},{"first_name":"Mergim","full_name":"Meta, Mergim","last_name":"Meta"},{"first_name":"Jan Laurenz","full_name":"Meidner, Jan Laurenz","last_name":"Meidner"},{"first_name":"Marvin","last_name":"Schwickert","full_name":"Schwickert, Marvin"},{"last_name":"Meyr","full_name":"Meyr, Jessica","first_name":"Jessica"},{"first_name":"Kevin","full_name":"Schwickert, Kevin","last_name":"Schwickert"},{"full_name":"Kersten, Christian","last_name":"Kersten","first_name":"Christian"},{"first_name":"Collin","full_name":"Zimmer, Collin","last_name":"Zimmer"},{"last_name":"Hammerschmidt","full_name":"Hammerschmidt, Stefan Josef","first_name":"Stefan Josef"},{"last_name":"Frey","full_name":"Frey, Ariane","first_name":"Ariane"},{"first_name":"Albin","last_name":"Lahu","full_name":"Lahu, Albin"},{"last_name":"de la Hoz-Rodríguez","full_name":"de la Hoz-Rodríguez, Sergio","first_name":"Sergio"},{"first_name":"Laura","full_name":"Agost-Beltrán, Laura","last_name":"Agost-Beltrán"},{"last_name":"Rodríguez","full_name":"Rodríguez, Santiago","first_name":"Santiago"},{"first_name":"Kira","full_name":"Diemer, Kira","last_name":"Diemer"},{"first_name":"Wilhelm","full_name":"Neumann, Wilhelm","last_name":"Neumann"},{"full_name":"Gonzàlez, Florenci V.","last_name":"Gonzàlez","first_name":"Florenci V."},{"first_name":"Bernd","full_name":"Engels, Bernd","last_name":"Engels"},{"first_name":"Tanja","full_name":"Schirmeister, Tanja","last_name":"Schirmeister"}],"publication_status":"published","date_created":"2024-01-04T08:24:31Z","doi":"10.3390/ijms24087226","volume":24,"project":[{"name":"PC2: Computing Resources Provided by the Paderborn Center for Parallel Computing","_id":"52"}]}