ArticleACS chemical biology2013
Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Extracellular Vesicle-Mediated Delivery of Constrained Peptides Disrupts the Pathogenic Interaction of LRRK2-FADD in Parkinson's Disease.Journal of extracellular biology · 2026Article
- Molecular mechanisms underlying HRK interaction with BCL-XL and BCL-2 reveal specificity determinants for BH3 mimetics.iScience · 2025Article
- Deciphering molecular specificity in MCL-1/BAK interaction and its implications for designing potent MCL-1 inhibitors.Cell death and differentiation · 2025Article
- Inhibitory Potential and Binding Thermodynamics of Scyllatoxin-Based BH3 Domain Mimetics Targeting Repressor BCL2 Proteins.Journal of molecular recognition : JMR · 2025Article
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Targeted Degradation of Protein Kinase A via a Stapled Peptide PROTAC.ACS chemical biology · 2024Article
- Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XNature communications · 2024Article
- Pore-forming proteins as drivers of membrane permeabilization in cell death pathways.Nature reviews. Molecular cell biology · 2023Review
- Rational design of stapled antimicrobial peptides.Amino acids · 2023Review
- Structural and ITC Characterization of Peptide-Protein Binding: Thermodynamic Consequences of Cyclization Constraints, a Case Study on Vascular Endothelial Growth Factor Ligands.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective.Frontiers in molecular biosciences · 2022Review
- Discovery, X-ray structure and CPP-conjugation enabled uptake of p53/MDM2 macrocyclic peptide inhibitors.RSC chemical biology · 2021Article
- Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Peptide-based inhibitors of protein-protein interactions: biophysical, structural and cellular consequences of introducing a constraint.Chemical science · 2021Review
- Directed evolution of cyclic peptides for inhibition of autophagy.Chemical science · 2021Article
- Macropinocytosis as a Key Determinant of Peptidomimetic Uptake in Cancer Cells.Journal of the American Chemical Society · 2020Article
- Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability.Chemical science · 2020Article
- N-locking stabilization of covalent helical peptides: Application to Bfl-1 antagonists.Chemical biology & drug design · 2020Article
- BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector Proteins.Cold Spring Harbor perspectives in biology · 2020Review
- Understanding Cell Penetration of Cyclic Peptides.Chemical reviews · 2019Review
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10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An attractive approach for developing therapeutic peptides is to enhance binding to their targets by stabilizing their α-helical conformation, for example, stabilized BimBH3 peptides (BimSAHB) designed to induce apoptosis. Unexpectedly, we found that such modified peptides have reduced affinity for their targets, the pro-survival Bcl-2 proteins. We attribute this loss in affinity to disruption of a network of stabilizing intramolecular interactions present in the bound state of the native peptide. Altering this network may compromise binding affinity, as in the case of the BimBH3 stapled peptide studied here. Moreover, cells exposed to these peptides do not readily undergo apoptosis, strongly indicating that BimSAHB is not inherently cell permeable.
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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.