Design of stapled α-helical peptides to specifically activate Wnt/β-catenin signaling

Cui, Hongyang; Zhao, Bing; Li, Yehua; Guo, Ye; Hu, Hao; Liu, Lei; Chen, Ye-Guang

doi:10.1038/cr.2013.30

Cited by 39 publications

(32 citation statements)

References 14 publications

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“…[234] It was shown that the correct subcellular localization is essential for efficient inhibition of the signaling cascade. [235] SAH-BCL9 B on the other hand proved effective in targeting the interaction between β-catenin and coactivator BCL9, thereby inhibiting a subset of Wnt target genes that was reported to control stem-cell-like behavior in some forms of cancer. SAH-BCL9 B reduced tumor growth, metathesis, and invasion in mouse xenograft models.…”

Section: Targeted Protein–protein Interactionsmentioning

confidence: 99%

“…Hydrocarbon-stapled peptides show enhanced a-helicity, improved protease stability, and, in many cases, increased cellular uptake compared to their natural precursors. [234][235][236][237] However, in some cases, extensive sequence optimization is required to ensure efficient cell permeability. [234,238] As a consequence of the robustness of the RCM reaction [239] and improved pharmacokinetic properties of hydrocarbon-stapled peptides, the technique was frequently applied for the stabilization of a-helical peptides and has proven particularly useful for the development of PPI inhibitors.…”

Section: A-methylated Hydrocarbon Cross-linksmentioning

confidence: 99%

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Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

et al. 2015

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Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.

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Section: Targeted Protein–protein Interactionsmentioning

confidence: 99%

Section: A-methylated Hydrocarbon Cross-linksmentioning

confidence: 99%

Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

et al. 2015

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“…Hydrocarbon‐Stapled‐Peptide wurden auch auf die Wnt‐Signalkaskade gerichtet 222. 234, 235, 413, 414 Der kanonische Wnt‐Signalweg wird durch die Bindung extrazellulärer Wnt‐Proteinliganden an einen Rezeptorkomplex aktiviert. Dadurch kommt es zur intrazellulären Inhibition eines Multiproteinzerstörungskomplexes, der aus Proteinen wie Axin und Proteinkinasen besteht.…”

Section: Protein‐protein‐interaktionsinhibitorenunclassified

Strukturbasierte Entwicklung von Protein‐Protein‐Interaktionsinhibitoren: Stabilisierung und Nachahmung von Peptidliganden

et al. 2015

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Protein‐Protein‐Interaktionen (PPIs) spielen auf allen Ebenen der Zellorganisation eine wichtige Rolle, was die Entwicklung von PPI‐Inhibitoren äußerst interessant macht. Die Herstellung von selektiven Inhibitoren ist wegen der relativ flachen und ausgedehnten Protein‐Protein‐Interaktionsflächen oftmals sehr aufwendig. Derartige Inhibitoren können beispielsweise durch das Nachahmen von Peptidliganden in deren bioaktiver Konformation generiert werden. Für die Entwicklung so genannter Peptidmimetika steht eine Reihe von Ansätzen zur Verfügung, die eine Ausrichtung der Seitenkettenfunktionalitäten in Analogie zu einer bestimmten Peptidsekundärstruktur ermöglichen. In diesem Aufsatz führen wir eine neue Klassifizierung von Peptidmimetika (Klasse A–D) ein, die eine klare Zuordnung der bestehenden Strategien erlaubt. Basierend auf dieser Klassifizierung werden Strategien erörtert, die bereits für ein strukturbasiertes Design von PPI‐Inhibitoren durch Stabilisierung oder Nachahmung von Kehren, β‐Faltblattstrukturen und Helices angewendet wurden.

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“…Moreover, when more than one disulfide surrogate need to be installed, the post-chain-assembly cyclization method may sometimes encounter difficulties in controlling the regioselectivity of the cross-linking reactions. [5] In our studies on bioactive peptidic macrocycles [6] we need to generate disulfide surrogates with a higher degree of structural diversity. Thus we became interested in the use of pre-prepared diaminodiacids in the synthesis of peptide disulfide bond mimics (Figure 1).…”

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confidence: 99%

Diaminodiacid‐Based Solid‐Phase Synthesis of Peptide Disulfide Bond Mimics

et al. 2013

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Design of stapled α-helical peptides to specifically activate Wnt/β-catenin signaling

Cited by 39 publications

References 14 publications

Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

Strukturbasierte Entwicklung von Protein‐Protein‐Interaktionsinhibitoren: Stabilisierung und Nachahmung von Peptidliganden

Diaminodiacid‐Based Solid‐Phase Synthesis of Peptide Disulfide Bond Mimics

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