ArticlePloS one2013
Truncated and helix-constrained peptides with high affinity and specificity for the cFos coiled-coil of AP-1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 53 citations in OpenAlex.
- Integrated metabolomic, cytotoxic, and computational investigation of Caralluma tuberculata extract in breast cancer cells.Scientific reports · 2026Article
- InsiliCoil: An Integrated Software Suite for Coiled Coil Design, Prediction, and Therapeutic Engineering.ACS synthetic biology · 2026Article
- Article
- A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The effect of helix-inducing constraints and downsizing upon a transcription block survival-derived functional cJun antagonist.Cell reports. Physical science · 2022Article
- Recent Applications of Retro-Inverso Peptides.International journal of molecular sciences · 2021Review
- Combined computational and intracellular peptide library screening: towards a potent and selective Fra1 inhibitor.RSC chemical biology · 2021Article
- Fortified Coiled Coils: Enhancing Mechanical Stability with Lactam or Metal Staples.Angewandte Chemie (International ed. in English) · 2021Article
- Stapled Peptides as HIF-1α/p300 Inhibitors: Helicity Enhancement in the Bound State Increases Inhibitory Potency.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Modulation of Coiled-Coil Binding Strength and Fusogenicity through Peptide Stapling.Bioconjugate chemistry · 2020Article
- Stapled Peptides-A Useful Improvement for Peptide-Based Drugs.Molecules (Basel, Switzerland) · 2019Review
- Structure determination of UL49.5 transmembrane protein from bovine herpesvirus 1 by NMR spectroscopy and molecular dynamics.Biochimica et biophysica acta. Biomembranes · 2019Article
- Constrained α-Helical Peptides as Inhibitors of Protein-Protein and Protein-DNA Interactions.Biomedicines · 2018Review
- Retro analog concept: comparative study on physico-chemical and biological properties of selected antimicrobial peptides.Amino acids · 2017Article
- Designing helical peptide inhibitors of protein-protein interactions.Current opinion in structural biology · 2016Review
- Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics.PloS one · 2016Article
- Swedish mutant APP-based BACE1 binding site peptide reduces APP β-cleavage and cerebral Aβ levels in Alzheimer's mice.Scientific reports · 2015Article
- Article
- Tightening up the structure, lighting up the pathway: Application of molecular constraints and light to manipulate protein folding, self-assembly and function.Science China. Chemistry · 2014Article
- Combining intracellular selection with protein-fragment complementation to derive Aβ interacting peptides.Protein engineering, design & selection : PEDS · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i→i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, α-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable α-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun-cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ∼9 kcal/mol, but this was compensated by increased conformational entropy (TΔS ≤7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by α-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases.
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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.