ArticleNature communications2023
Amide-to-ester substitution as a stable alternative to N-methylation for increasing membrane permeability in cyclic peptides.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
26 citing papers in PubMed, 60 citations in OpenAlex.
- Biosynthetic origin of anticancer dolastatin 15 reveals a noncanonical NRPS architecture enabling 2-keto acid activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Backbone Steric Constraints Underlie High Passive Membrane Permeability of N-Alkyl Peptides.Angewandte Chemie (International ed. in English) · 2026Article
- Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.Journal of medicinal chemistry · 2026Review
- A decoupled alignment kernel for peptide membrane permeability predictions.Journal of cheminformatics · 2026Article
- What Is in a Structure? Cell Permeability and Solubility of Series of Macrocycles and Linear Matched Pairs.Journal of medicinal chemistry · 2026Article
- Linker Engineering in Stapled Peptides for Enhanced Membrane Permeability: Screening and Optimization Strategies.International journal of molecular sciences · 2026Review
- Diastereomeric Branched-Ester dBET1 Analogs Exhibit Conformation-Dependent Differences in Passive Membrane Permeability.Journal of medicinal chemistry · 2026Article
- Paraisariamides: Cycloheptapeptide Toxins from Entomopathogenic Fungi (Journal of natural products · 2026Article
- Recent Advances in Cyclic Peptide-Based Therapeutic Strategies for Renal Cell Carcinoma: A Focused Review.Drug design, development and therapy · 2026Review
- Recent advances in the cleavage of non-activated amides.Beilstein journal of organic chemistry · 2026Review
- Rational design and applications of piperazine and cyclohexane ionizable lipids for PKU and SSADH deficiency.Molecular therapy. Nucleic acids · 2025Article
- C2PO: an ML-powered optimizer of the membrane permeability of cyclic peptides through chemical modification.Journal of cheminformatics · 2025Article
- Challenges of Aufheben to Promote Druglikeness: Chemical Modification Strategies to Improve Aqueous Solubility and Permeability.Journal of medicinal chemistry · 2025Review
- Temporal and Spatial Characterization of CUL3ACS chemical biology · 2025Article
- Systematic benchmarking of 13 AI methods for predicting cyclic peptide membrane permeability.Journal of cheminformatics · 2025Article
- MultiCycPermea: accurate and interpretable prediction of cyclic peptide permeability using a multimodal image-sequence model.BMC biology · 2025Article
- α-Triazolylboronic Acids: A Novel Scaffold to Target FLT3 in AML.ChemMedChem · 2025Article
- Selection of Nucleotide-Encoded Mass Libraries of Macrocyclic Peptides for Inaccessible Drug Targets.Chemical reviews · 2024Review
- Mammalian Esterase Activity: Implications for Peptide Prodrugs.Biochemistry · 2024Article
- CycPeptMP: enhancing membrane permeability prediction of cyclic peptides with multi-level molecular features and data augmentation.Briefings in bioinformatics · 2024Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Naturally occurring peptides with high membrane permeability often have ester bonds on their backbones. However, the impact of amide-to-ester substitutions on the membrane permeability of peptides has not been directly evaluated. Here we report the effect of amide-to-ester substitutions on the membrane permeability and conformational ensemble of cyclic peptides related to membrane permeation. Amide-to-ester substitutions are shown to improve the membrane permeability of dipeptides and a model cyclic hexapeptide. NMR-based conformational analysis and enhanced sampling molecular dynamics simulations suggest that the conformational transition of the cyclic hexapeptide upon membrane permeation is differently influenced by an amide-to-ester substitution and an amide N-methylation. The effect of amide-to-ester substitution on membrane permeability of other cyclic hexapeptides, cyclic octapeptides, and a cyclic nonapeptide is also investigated to examine the scope of the substitution. Appropriate utilization of amide-to-ester substitution based on our results will facilitate the development of membrane-permeable peptides.
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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.