---
_id: '50150'
abstract:
- lang: eng
text: 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.
article_number: '7226'
author:
- first_name: Patrick
full_name: Müller, Patrick
last_name: Müller
- 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
full_name: Schwickert, Marvin
last_name: Schwickert
- first_name: Jessica
full_name: Meyr, Jessica
last_name: Meyr
- first_name: Kevin
full_name: Schwickert, Kevin
last_name: Schwickert
- first_name: Christian
full_name: Kersten, Christian
last_name: Kersten
- first_name: Collin
full_name: Zimmer, Collin
last_name: Zimmer
- first_name: Stefan Josef
full_name: Hammerschmidt, Stefan Josef
last_name: Hammerschmidt
- first_name: Ariane
full_name: Frey, Ariane
last_name: Frey
- first_name: Albin
full_name: Lahu, Albin
last_name: Lahu
- first_name: Sergio
full_name: de la Hoz-Rodríguez, Sergio
last_name: de la Hoz-Rodríguez
- first_name: Laura
full_name: Agost-Beltrán, Laura
last_name: Agost-Beltrán
- first_name: Santiago
full_name: Rodríguez, Santiago
last_name: Rodríguez
- first_name: Kira
full_name: Diemer, Kira
last_name: Diemer
- first_name: Wilhelm
full_name: Neumann, Wilhelm
last_name: Neumann
- first_name: Florenci V.
full_name: Gonzàlez, Florenci V.
last_name: Gonzàlez
- first_name: Bernd
full_name: Engels, Bernd
last_name: Engels
- first_name: Tanja
full_name: Schirmeister, Tanja
last_name: Schirmeister
citation:
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. International Journal of Molecular Sciences. 2023;24(8).
doi:10.3390/ijms24087226
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., & Schirmeister, T. (2023). Investigation of the Compatibility
between Warheads and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive
Reactivity and Selectivity Study. International Journal of Molecular Sciences,
24(8), Article 7226. https://doi.org/10.3390/ijms24087226
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={10.3390/ijms24087226},
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.” International Journal of Molecular Sciences
24, no. 8 (2023). https://doi.org/10.3390/ijms24087226.
ieee: 'P. Müller et al., “Investigation of the Compatibility between Warheads
and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity
and Selectivity Study,” International Journal of Molecular Sciences, vol.
24, no. 8, Art. no. 7226, 2023, doi: 10.3390/ijms24087226.'
mla: Müller, Patrick, et al. “Investigation of the Compatibility between Warheads
and Peptidomimetic Sequences of Protease Inhibitors—A Comprehensive Reactivity
and Selectivity Study.” International Journal of Molecular Sciences, vol.
24, no. 8, 7226, MDPI AG, 2023, doi:10.3390/ijms24087226.
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).
date_created: 2024-01-04T08:24:31Z
date_updated: 2024-01-05T12:59:32Z
doi: 10.3390/ijms24087226
intvolume: ' 24'
issue: '8'
keyword:
- Inorganic Chemistry
- Organic Chemistry
- Physical and Theoretical Chemistry
- Computer Science Applications
- Spectroscopy
- Molecular Biology
- General Medicine
- Catalysis
language:
- iso: eng
project:
- _id: '52'
name: 'PC2: Computing Resources Provided by the Paderborn Center for Parallel Computing'
publication: International Journal of Molecular Sciences
publication_identifier:
issn:
- 1422-0067
publication_status: published
publisher: MDPI AG
status: public
title: Investigation of the Compatibility between Warheads and Peptidomimetic Sequences
of Protease Inhibitors—A Comprehensive Reactivity and Selectivity Study
type: journal_article
user_id: '67287'
volume: 24
year: '2023'
...