Targeting the Genome‐Stability Hub Ctf4 by Stapled‐Peptide Design

Wu, Yinghai; Villa, Fabrizio; Maman, Joseph D.; Lau, Yu Heng; Simon, Aline C.; Labib, Karim; Spring, David R.; Pellegrini, Luca

doi:10.1002/ange.201705611

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…Spring et al also used the azido alkynyl stapling method to develop an ⍺‐helical peptide with the ability to bind to Ctf4. Interestingly, the authors constrained the peptide at the i, i+6 positions, and this arrangement gave good helicity and target binding affinity …”

Section: Constraint Functionalization and Diversificationmentioning

confidence: 99%

Recent structural advances in constrained helical peptides

Skowron

Speltz

Moore

2018

Medicinal Research Reviews

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Given the ubiquity of the ⍺-helix in the proteome, there has been much research in developing mimics of ⍺-helices, and most of this study has been toward developing proteinprotein interaction inhibitors. A common strategy for mimicking ⍺-helices has been through the use of constrained, helical peptides. The addition of a constraint typically provides for conformational and proteolytic stability and, in some cases, cell permeability. Some of the most well-known strategies included are lactam formation and hydrocarbon "stapling." Beyond those strategies, there have been many recent advances in developing constrained peptides. The purpose of this review is to highlight recent advances in the development of new helix-stabilizing technologies, constraint diversification strategies, tether diversification strategies, and combination strategies that create new bicyclic helical peptides. K E Y W O R D S alpha helix, helical peptides, peptide chemistry, protein-protein interactions 1 | INTRODUCTIONThere are a multitude of protein-protein interactions in the cell that are mediated by ⍺-helices, and in many disease states it would be advantageous to mimic features of an ⍺-helix with a small molecule or peptide. A common strategy for mimicking ⍺-helices has been through the use of constrained, helical peptides. 1-9 Doing so provides for conformational stability by reducing the number of degrees of freedom of the peptide and/or by facilitating ⍺-helical hydrogen bonding. This strategy also often provides for proteolytic stability: many proteases recognize an extended peptide conformation, but because of the conformational rigidity imparted by the constraint, helical peptides are not readily recognized by proteases that otherwise might recognize an Med Res Rev. 2019;39:749-770.wileyonlinelibrary.com/journal/med

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Section: Constraint Functionalization and Diversificationmentioning

confidence: 99%

Recent structural advances in constrained helical peptides

Skowron

Speltz

Moore

2018

Medicinal Research Reviews

View full text Add to dashboard Cite

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Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

et al. 2020

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Herein, we report the photoinitiated polymerizationinduced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles.T he one-pot synthetic approachy ielded micellar nanoparticles at high concentrations and at scale (150 mg mL À1)w ith tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks.C ritically,t he peptide-functionalized nanoparticles imbued the proapoptotic "KLA" peptides (amino acid sequence:KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent displayof KLA peptide brushes.T he result was demonstrated improved apoptosis efficiency in HeLa cells.T hese results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.

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Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

et al. 2020

View full text Add to dashboard Cite

Herein, we report the photoinitiated polymerizationinduced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL À1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic "KLA" peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.

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Targeting the Genome‐Stability Hub Ctf4 by Stapled‐Peptide Design

Cited by 3 publications

References 38 publications

Recent structural advances in constrained helical peptides

Recent structural advances in constrained helical peptides

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

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