Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Quambusch, Lena | - |
dc.contributor.author | Landel, Ina | - |
dc.contributor.author | Depta, Laura | - |
dc.contributor.author | Weisner, Jörn | - |
dc.contributor.author | Uhlenbrock, Niklas | - |
dc.contributor.author | Müller, Matthias P. | - |
dc.contributor.author | Glanemann, Franziska | - |
dc.contributor.author | Althoff, Kristina | - |
dc.contributor.author | Siveke, Jens T. | - |
dc.contributor.author | Rauh, Daniel | - |
dc.date.accessioned | 2020-03-05T13:19:32Z | - |
dc.date.available | 2020-03-05T13:19:32Z | - |
dc.date.issued | 2019-10-04 | - |
dc.identifier.uri | http://hdl.handle.net/2003/39033 | - |
dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-20952 | - |
dc.description.abstract | Isoforms of protein kinase Akt are involved in essential processes including cell proliferation, survival, and metabolism. However, their individual roles in health and disease have not been thoroughly evaluated. Thus, there is an urgent need for perturbation studies, preferably mediated by highly selective bioactive small molecules. Herein, we present a structure‐guided approach for the design of structurally diverse and pharmacologically beneficial covalent‐allosteric modifiers, which enabled an investigation of the isoform‐specific preferences and the important residues within the allosteric site of the different isoforms. The biochemical, cellular, and structural evaluations revealed interactions responsible for the selective binding profiles. The isoform‐selective covalent‐allosteric Akt inhibitors that emerged from this approach showed a conclusive structure–activity relationship and broke ground in the development of selective probes to delineate the isoform‐specific functions of Akt kinases. | en |
dc.language.iso | en | de |
dc.relation.ispartofseries | Angewandte Chemie International Edition;Vol. 58, Issue 52, 18823-18829 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | Akt isoforms | en |
dc.subject | Allosteric sites | en |
dc.subject | Cancer | en |
dc.subject | Covalent inhibitors | en |
dc.subject | Isoform selectivity | en |
dc.subject.ddc | 570 | - |
dc.subject.ddc | 540 | - |
dc.title | Covalent-allosteric inhibitors to achieve akt isoform-selectivity | en |
dc.type | Text | de |
dc.type.publicationtype | article | de |
dcterms.accessRights | open access | - |
eldorado.secondarypublication | true | de |
eldorado.secondarypublication.primaryidentifier | https://doi.org/10.1002/anie.201909857 | de |
eldorado.secondarypublication.primarycitation | Angewandte Chemie International Edition. Vol. 58, 2019, Issue 52, 8823 –18829 | de |
Appears in Collections: | Medizinische Chemie und Chemische Biologie |
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File | Description | Size | Format | |
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Quambusch_et_al-2019-Angewandte_Chemie_International_Edition.pdf | DNB | 5.15 MB | Adobe PDF | View/Open |
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