ArticleJournal of medicinal chemistry2023
Lessons for Oral Bioavailability: How Conformationally Flexible Cyclic Peptides Enter and Cross Lipid Membranes.
Article in Journal of medicinal chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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
31 citing papers in PubMed.
- Advances in Cyclic Peptides Targeting G Protein-Coupled Receptors.Chembiochem : a European journal of chemical biology · 2026Review
- Dynamics of (Hetero)aryl Motifs: An Integrative Approach To Study the Conformational Landscape in Macrocycles.Journal of the American Chemical Society · 2026Article
- ChemBioParis 2025: Approaching Biology Through Chemistry in the City of Light.Chembiochem : a European journal of chemical biology · 2026Article
- Article
- Structure-Guided Design of an Interface-Derived Inhibitor Peptide Against Spodoptera frugiperda Digestive Trypsins.Archives of insect biochemistry and physiology · 2026Article
- Fluorination augments tumor engagement and antitumor immunity of a D-peptide-based radiotheranostic agent for combinatorial immune checkpoint blockade therapy.Journal for immunotherapy of cancer · 2026Article
- From Membrane Composition to Antimicrobial Strategies: Experimental and Computational Approaches to AMP Design and Selectivity.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Arginase 1 promotes hepatic lipogenesis by regulating ERK2/PPARγ signaling in a non-canonical manner.Nature communications · 2026Article
- Overcoming Oral Cavity Barriers for Peptide Delivery Using Advanced Pharmaceutical Techniques and Nano-Formulation Platforms.Biomedicines · 2025Review
- Permeation enhancer-induced membrane defects assist the oral absorption of peptide drugs.Nature communications · 2025Article
- Marine Bioactive Peptides in the Regulation of Inflammatory Responses: Current Trends and Future Directions.Proteomes · 2025Review
- Systematic Determination of the Impact of Structural Edits on Peptide Accumulation into Mycobacteria.ACS chemical biology · 2025Article
- Chemical Properties, Preparation, and Pharmaceutical Effects of Cyclic Peptides fromMolecules (Basel, Switzerland) · 2025Review
- Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines.Signal transduction and targeted therapy · 2025Review
- Natural Cyclic Peptides: Synthetic Strategies and Biomedical Applications.Biomedicines · 2025Review
- Cyclic peptide membrane permeability prediction using deep learning model based on molecular attention transformer.Frontiers in bioinformatics · 2025Article
- Chromatographic Determination of Permeability-Relevant Lipophilicity Facilitates Rapid Analysis of Macrocyclic Peptide Scaffolds.Journal of medicinal chemistry · 2024Article
- Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC - What is Coming Next?Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- CREMP: Conformer-rotamer ensembles of macrocyclic peptides for machine learning.Scientific data · 2024Article
- Leveraging Machine Learning-Guided Molecular Simulations Coupled with Experimental Data to Decipher Membrane Binding Mechanisms of Aminosterols.Journal of chemical theory and computation · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Cyclic peptides extend the druggable target space due to their size, flexibility, and hydrogen-bonding capacity. However, these properties impact also their passive membrane permeability. As the "journey" through membranes cannot be monitored experimentally, little is known about the underlying process, which hinders rational design. Here, we use molecular simulations to uncover how cyclic peptides permeate a membrane. We show that side chains can act as "molecular anchors", establishing the first contact with the membrane and enabling insertion. Once inside, the peptides are positioned between headgroups and lipid tails─a unique polar/apolar interface. Only one of two distinct orientations at this interface allows for the formation of the permeable "closed" conformation. In the closed conformation, the peptide crosses to the lower leaflet via another "anchoring" and flipping mechanism. Our findings provide atomistic insights into the permeation process of flexible cyclic peptides and reveal design considerations for each step of the process.
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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.