Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Gall, Flavio | - |
dc.contributor.author | Hohl, Deborah | - |
dc.contributor.author | Frasson, David | - |
dc.contributor.author | Wermelinger, Tobias | - |
dc.contributor.author | Mittl, Peer R. E. | - |
dc.contributor.author | Sievers, Martin | - |
dc.contributor.author | Riedl, Rainer | - |
dc.date.accessioned | 2021-02-18T10:43:18Z | - |
dc.date.available | 2021-02-18T10:43:18Z | - |
dc.date.issued | 2019-01-07 | - |
dc.identifier.issn | 1433-7851 | de_CH |
dc.identifier.issn | 1521-3773 | de_CH |
dc.identifier.uri | https://digitalcollection.zhaw.ch/handle/11475/21751 | - |
dc.description.abstract | De novo drug discovery is still a challenge in the search for potent and selective modulators of therapeutically relevant target proteins. Here, we disclose the unexpected discovery of a peptidic ligand 1 by X-ray crystallography, which was auto-tailored by the therapeutic target MMP-13 through partial self-degradation and subsequent structure-based optimization to a highly potent and selective β-sheet peptidomimetic inhibitor derived from the endogenous tissue inhibitors of metalloproteinases (TIMPs). The incorporation of non-proteinogenic amino acids in combination with a cyclization strategy proved to be key for the de novo design of TIMP peptidomimetics. The optimized cyclic peptide 4 (ZHAWOC7726) is membrane permeable with an IC50 of 21 nm for MMP-13 and an attractive selectivity profile with respect to a polypharmacology approach including the anticancer targets MMP-2 (IC50 : 170 nm) and MMP-9 (IC50 : 140 nm). | de_CH |
dc.language.iso | en | de_CH |
dc.publisher | Wiley | de_CH |
dc.relation.ispartof | Angewandte Chemie: International Edition | de_CH |
dc.rights | Licence according to publishing contract | de_CH |
dc.subject | Drug design | de_CH |
dc.subject | Medicinal chemistry | de_CH |
dc.subject | Peptidomimetics | de_CH |
dc.subject | Structural biology | de_CH |
dc.subject | Structure-activity relationship | de_CH |
dc.subject | Binding sites | de_CH |
dc.subject | Crystallography | de_CH |
dc.subject | Cyclization | de_CH |
dc.subject | Matrix metalloproteinase 13 | de_CH |
dc.subject | Matrix metalloproteinase inhibitors | de_CH |
dc.subject | Molecular dynamics simulation | de_CH |
dc.subject | Cyclic peptides | de_CH |
dc.subject | Peptidomimetics | de_CH |
dc.subject | Protease inhibitors | de_CH |
dc.subject | Tissue inhibitor of metalloproteinases | de_CH |
dc.subject | X-Ray | de_CH |
dc.subject.ddc | 615: Pharmakologie und Therapeutik | de_CH |
dc.title | Drug design inspired by nature : crystallographic detection of an auto‐tailored protease inhibitor template | de_CH |
dc.type | Beitrag in wissenschaftlicher Zeitschrift | de_CH |
dcterms.type | Text | de_CH |
zhaw.departement | Life Sciences und Facility Management | de_CH |
zhaw.organisationalunit | Institut für Chemie und Biotechnologie (ICBT) | de_CH |
dc.identifier.doi | 10.1002/anie.201812348 | de_CH |
dc.identifier.pmid | 30615822 | de_CH |
zhaw.funding.eu | No | de_CH |
zhaw.issue | 12 | de_CH |
zhaw.originated.zhaw | Yes | de_CH |
zhaw.pages.end | 4055 | de_CH |
zhaw.pages.start | 4051 | de_CH |
zhaw.publication.status | publishedVersion | de_CH |
zhaw.volume | 58 | de_CH |
zhaw.publication.review | Peer review (Publikation) | de_CH |
zhaw.webfeed | CC Drug Discovery | de_CH |
zhaw.author.additional | No | de_CH |
zhaw.display.portrait | Yes | de_CH |
Appears in collections: | Publikationen Life Sciences und Facility Management |
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Gall, F., Hohl, D., Frasson, D., Wermelinger, T., Mittl, P. R. E., Sievers, M., & Riedl, R. (2019). Drug design inspired by nature : crystallographic detection of an auto‐tailored protease inhibitor template. Angewandte Chemie: International Edition, 58(12), 4051–4055. https://doi.org/10.1002/anie.201812348
Gall, F. et al. (2019) ‘Drug design inspired by nature : crystallographic detection of an auto‐tailored protease inhibitor template’, Angewandte Chemie: International Edition, 58(12), pp. 4051–4055. Available at: https://doi.org/10.1002/anie.201812348.
F. Gall et al., “Drug design inspired by nature : crystallographic detection of an auto‐tailored protease inhibitor template,” Angewandte Chemie: International Edition, vol. 58, no. 12, pp. 4051–4055, Jan. 2019, doi: 10.1002/anie.201812348.
GALL, Flavio, Deborah HOHL, David FRASSON, Tobias WERMELINGER, Peer R. E. MITTL, Martin SIEVERS und Rainer RIEDL, 2019. Drug design inspired by nature : crystallographic detection of an auto‐tailored protease inhibitor template. Angewandte Chemie: International Edition. 7 Januar 2019. Bd. 58, Nr. 12, S. 4051–4055. DOI 10.1002/anie.201812348
Gall, Flavio, Deborah Hohl, David Frasson, Tobias Wermelinger, Peer R. E. Mittl, Martin Sievers, and Rainer Riedl. 2019. “Drug Design Inspired by Nature : Crystallographic Detection of an Auto‐Tailored Protease Inhibitor Template.” Angewandte Chemie: International Edition 58 (12): 4051–55. https://doi.org/10.1002/anie.201812348.
Gall, Flavio, et al. “Drug Design Inspired by Nature : Crystallographic Detection of an Auto‐Tailored Protease Inhibitor Template.” Angewandte Chemie: International Edition, vol. 58, no. 12, Jan. 2019, pp. 4051–55, https://doi.org/10.1002/anie.201812348.
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