ArticleBiophysical journal2013
Membrane permeability of hydrocarbon-cross-linked peptides.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Optimization of stapled peptide inhibitors reveals design principles for targeting talin-induced integrin activation.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of talin-induced integrin activation by a double-hit stapled peptide.Structure (London, England : 1993) · 2023Article
- Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress.Biomedicines · 2023Review
- Peptide-based inhibitors of protein-protein interactions: biophysical, structural and cellular consequences of introducing a constraint.Chemical science · 2021Review
- Strategies to expand peptide functionality through hybridisation with a small molecule component.RSC chemical biology · 2021Review
- Understanding Cell Penetration of Cyclic Peptides.Chemical reviews · 2019Review
- Article
- Tyrosine Hydroxylase Binding to Phospholipid Membranes Prompts Its Amyloid Aggregation and Compromises Bilayer Integrity.Scientific reports · 2016Article
- Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices.Nature chemical biology · 2016Article
- Pro-apoptotic Bax molecules densely populate the edges of membrane pores.Scientific reports · 2016Article
- Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes.Angewandte Chemie (International ed. in English) · 2015Review
- The Atlastin C-terminal tail is an amphipathic helix that perturbs the bilayer structure during endoplasmic reticulum homotypic fusion.The Journal of biological chemistry · 2015Article
- Dual-acting stapled peptides target both HIV-1 entry and assembly.Retrovirology · 2013Article
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Authors and funding
4 authors.
Funding
Abstract
Schafmeister, Po, and Verdine (another study) introduced a method using a hydrocarbon linker (staple) to stabilize a peptide in a helical configuration. One intended goal of this scheme is to facilitate the delivery of peptide drugs into target cells. Here, we investigate whether stapled peptides are intrinsically membrane permeable, by performing a case study on a stapled 12-mer peptide named NYAD-1. We found that the native peptide CAI (an HIV-1 inhibitor) does not bind to lipid bilayers, however NYAD-1 indeed permeates through lipid bilayers even at low solution concentrations. To understand the reason for the membrane permeability, we investigated the physical properties of NYAD-1 as a function of bound peptide/lipid molar ratio P/L. We found that NYAD-1 spontaneously binds to a lipid bilayer. At low P/L, the peptide primarily binds on the polar-apolar interface with its helical axis parallel to the bilayer, which has the effect of stretching the membrane area and thinning the membrane. The membrane thinning reaches its maximum at P/L ∼1/15-1/12 in DOPC bilayers. Additional bound peptides have little thinning effect and their helical axes are normal to the plane of bilayers. Thus, the stapled peptide has a membrane interaction behavior similar to helical antimicrobial peptides, such as magainin and melittin. We emphasize that not all peptides that bind to lipid bilayers in the α-helical form behave this way.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.