ArticlePloS one2014
Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed.
- Sequence Engineering at Non-motif Modulator Residues Yields a Peptide That Effectively Targets a Single PDZ Protein in a Disease-relevant Cellular Context.Journal of molecular biology · 2026Article
- Sequence engineering at non-motif modulator residues yields a peptide that effectively targets a single PDZ protein in a disease-relevant cellular context.bioRxiv : the preprint server for biology · 2025Article
- Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.Protein science : a publication of the Protein Society · 2023Article
- Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.bioRxiv : the preprint server for biology · 2023Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Highway to Cell: Selection of the Best Cell-Penetrating Peptide to Internalize the CFTR-Stabilizing iCAL36 Peptide.Pharmaceutics · 2022Article
- Intestinal secretory mechanisms and diarrhea.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Cyclic Peptidyl Inhibitors against CAL/CFTR Interaction for Treatment of Cystic Fibrosis.Journal of medicinal chemistry · 2020Article
- Computational Analysis of Energy Landscapes Reveals Dynamic Features That Contribute to Binding of Inhibitors to CFTR-Associated Ligand.The journal of physical chemistry. B · 2019Article
- MotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity.Protein science : a publication of the Protein Society · 2019Article
- PDZ Domains as Drug Targets.Advanced therapeutics · 2019Review
- Improved Modeling of Halogenated Ligand-Protein Interactions Using the Drude Polarizable and CHARMM Additive Empirical Force Fields.Journal of chemical information and modeling · 2019Article
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Toward inclusive therapy with CFTR modulators: Progress and challenges.Pediatric pulmonology · 2017Review
- CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia.International journal of molecular sciences · 2017Review
- Acetylation of C/EBPα inhibits its granulopoietic function.Nature communications · 2016Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
PDZ domains are protein-protein interaction modules that coordinate multiple signaling and trafficking pathways in the cell and that include active therapeutic targets for diseases such as cancer, cystic fibrosis, and addiction. Our previous work characterized a PDZ interaction that restricts the apical membrane half-life of the cystic fibrosis transmembrane conductance regulator (CFTR). Using iterative cycles of peptide-array and solution-binding analysis, we targeted the PDZ domain of the CFTR-Associated Ligand (CAL), and showed that an engineered peptide inhibitor rescues cell-surface expression of the most common CFTR disease mutation ΔF508. Here, we present a series of scaffolds containing chemically modifiable side chains at all non-motif positions along the CAL PDZ domain binding cleft. Concordant equilibrium dissociation constants were determined in parallel by fluorescence polarization, isothermal titration calorimetry, and surface plasmon resonance techniques, confirming robust affinity for each scaffold and revealing an enthalpically driven mode of inhibitor binding. Structural studies demonstrate a conserved binding mode for each peptide, opening the possibility of combinatorial modification. Finally, we diversified one of our peptide scaffolds with halogenated substituents that yielded modest increases in binding affinity. Overall, this work validates our approach and provides a stereochemical foundation for further CAL inhibitor design and screening.
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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.