Constrained Peptides with Fine‐Tuned Flexibility Inhibit NF‐Y Transcription Factor Assembly
Abstract: Protein complex formation depends on the interplay between preorganization and flexibility of the binding epitopes involved. The design of epitope mimetics typically focuses on stabilizing a particular bioactive conformation, often without considering conformational dynamics, which limits the potential of peptidomimetics against challenging targets such as transcription factors. We developed a peptide‐derived inhibitor of the NF‐Y transcription factor by first constraining the conformation of an epitope through hydrocarbon stapling and then fine‐tuning its flexibility. In the initial set of constrained peptides, a single non‐interacting α‐methyl group was observed to have a detrimental effect on complex stability. Biophysical characterization revealed how this methyl group affects the conformation of the peptide in its bound state. Adaption of the methylation pattern resulted in a peptide that inhibits transcription factor assembly and subsequent recruitment to the target DNA.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Constrained Peptides with Fine‐Tuned Flexibility Inhibit NF‐Y Transcription Factor Assembly ; volume:58 ; number:48 ; year:2019 ; pages:17351-17358 ; extent:8
Angewandte Chemie / International edition. International edition ; 58, Heft 48 (2019), 17351-17358 (gesamt 8)
- Creator
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Jeganathan, Sadasivam
Wendt, Mathias
Kiehstaller, Sebastian
Brancaccio, Diego
Kuepper, Arne
Pospiech, Nicole
Carotenuto, Alfonso
Novellino, Ettore
Hennig, Sven
Großmann, Tom N.
- DOI
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10.1002/anie.201907901
- URN
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urn:nbn:de:101:1-2022080613150252911835
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:27 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Jeganathan, Sadasivam
- Wendt, Mathias
- Kiehstaller, Sebastian
- Brancaccio, Diego
- Kuepper, Arne
- Pospiech, Nicole
- Carotenuto, Alfonso
- Novellino, Ettore
- Hennig, Sven
- Großmann, Tom N.
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Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Multicomponent cyclization strategies to novel conformationally constrained peptides
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Human peptides α-defensin-1 and -5 inhibit pertussis toxin
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