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.
- Standort
-
Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
-
Online-Ressource
- Sprache
-
Englisch
- Erschienen in
-
Constrained Peptides with Fine‐Tuned Flexibility Inhibit NF‐Y Transcription Factor Assembly ; volume:131 ; number:48 ; year:2019 ; pages:17512-17519 ; extent:8
Angewandte Chemie ; 131, Heft 48 (2019), 17512-17519 (gesamt 8)
- Urheber
-
Jeganathan, Sadasivam
Wendt, Mathias
Kiehstaller, Sebastian
Brancaccio, Diego
Kuepper, Arne
Pospiech, Nicole
Carotenuto, Alfonso
Novellino, Ettore
Hennig, Sven
Großmann, Tom N.
- DOI
-
10.1002/ange.201907901
- URN
-
urn:nbn:de:101:1-2022081006415680879150
- Rechteinformation
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
15.08.2025, 07:27 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Jeganathan, Sadasivam
- Wendt, Mathias
- Kiehstaller, Sebastian
- Brancaccio, Diego
- Kuepper, Arne
- Pospiech, Nicole
- Carotenuto, Alfonso
- Novellino, Ettore
- Hennig, Sven
- Großmann, Tom N.
Ähnliche Objekte (12)
Constrained Peptides with Fine‐Tuned Flexibility Inhibit NF‐Y Transcription Factor Assembly
A Matter of Charge: Electrostatically Tuned Coassembly of Amphiphilic Peptides
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Multicomponent cyclization strategies to novel conformationally constrained peptides
Recognition of ASF1 by Using Hydrocarbon‐Constrained Peptides
Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis
Human peptides α-defensin-1 and -5 inhibit pertussis toxin
Enantiomeric Aβ peptides inhibit the fluid shear stress response of PIEZO1
Does Employment Protection Inhibit Labor Market Flexibility? Lessons from Germany, France and Belgium
Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells
Stay Tuned (DT); Stay Tuned (OT) (Land: USA, Regie: Peter Hyams)
Constrained Peptides with Fine‐Tuned Flexibility Inhibit NF‐Y Transcription Factor Assembly
A Matter of Charge: Electrostatically Tuned Coassembly of Amphiphilic Peptides
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Multicomponent cyclization strategies to novel conformationally constrained peptides
Recognition of ASF1 by Using Hydrocarbon‐Constrained Peptides
Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis
Human peptides α-defensin-1 and -5 inhibit pertussis toxin
Enantiomeric Aβ peptides inhibit the fluid shear stress response of PIEZO1
Does Employment Protection Inhibit Labor Market Flexibility? Lessons from Germany, France and Belgium
Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells
Stay Tuned (DT); Stay Tuned (OT) (Land: USA, Regie: Peter Hyams)
Constrained Peptides with Fine‐Tuned Flexibility Inhibit NF‐Y Transcription Factor Assembly
A Matter of Charge: Electrostatically Tuned Coassembly of Amphiphilic Peptides
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Multicomponent cyclization strategies to novel conformationally constrained peptides
Recognition of ASF1 by Using Hydrocarbon‐Constrained Peptides
Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis
Human peptides α-defensin-1 and -5 inhibit pertussis toxin
Enantiomeric Aβ peptides inhibit the fluid shear stress response of PIEZO1
Does Employment Protection Inhibit Labor Market Flexibility? Lessons from Germany, France and Belgium
Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells