ArticleOrganic & biomolecular chemistry2018
Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect.
Article in Organic & biomolecular chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Folded-state compatibility and unfolded-state constraint govern staple-based stabilization: guidelines from a coiled-coil model.RSC chemical biology · 2026Article
- Stapling of β-Glucans Increases Antibody Binding.Journal of the American Chemical Society · 2025Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- The Effect of PEGylation on Drugs' Pharmacokinetic Parameters; from Absorption to Excretion.Current drug delivery · 2024Review
- Structural guidelines for stabilization of α-helical coiled coilsRSC chemical biology · 2022Article
- Long-range PEG Stapling: Macrocyclization for Increased Protein Conformational Stability and Resistance to Proteolysis.RSC chemical biology · 2020Article
- Proteomimetics as protein-inspired scaffolds with defined tertiary folding patterns.Nature chemistry · 2020Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Hydrocarbon stapling and PEGylation are distinct strategies for enhancing the conformational stability and/or pharmacokinetic properties of peptide and protein drugs. Here we combine these approaches by incorporating asparagine-linked O-allyl PEG oligomers at two positions within the β-sheet protein WW, followed by stapling of the PEGs via olefin metathesis. The impact of stapling two sites that are close in primary sequence is small relative to the impact of PEGylation alone and depends strongly on PEG length. In contrast, stapling of two PEGs that are far apart in primary sequence but close in tertiary structure provides substantially more stabilization, derived mostly from an entropic effect. Comparison of PEGylation + stapling vs. alkylation + stapling at the same positions in WW reveals that both approaches provide similar overall levels of conformational stability.
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Registered trials
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