ArticleNature chemical biology2011
On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
What it found
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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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Who cites it
126 citing papers in PubMed, 376 citations in OpenAlex.
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- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.Journal of medicinal chemistry · 2026Review
- Late-Stage Functionalization of Peptides on the Solid Phase.Angewandte Chemie (International ed. in English) · 2026Review
- What Is in a Structure? Cell Permeability and Solubility of Series of Macrocycles and Linear Matched Pairs.Journal of medicinal chemistry · 2026Article
- Peptomer Linkers Enable Kinetic Control over Co-Delivery of Multiple Chemotherapeutics.Advanced healthcare materials · 2026Article
- Making Blank Faces Expressive: Chemical Approaches to the Modification of Chemically Inert Peptides.Journal of peptide science : an official publication of the European Peptide Society · 2026Review
- A generalizable assay for intracellular accumulation to profile cytosolic drug delivery in mammalian cells.Communications chemistry · 2026Article
- Enhanced antibacterial activity of antimicrobial peptide-antibiotic combinations against multidrug-resistant bacteria.FEMS microbes · 2026Review
- Flexible molecular chameleons: structural adaptability and therapeutic applications.Frontiers in chemistry · 2026Review
- Rational Activity Improvement of Cyclic Peptides through Stabilization and Rigidification of Main Chain Using φ/ψ Plots of Amino Acids.ACS omega · 2025Article
- Backbone Alterations in Cyclic Peptides Influence Both Membrane Permeability and Biological Activity.Journal of medicinal chemistry · 2025Article
- Challenges of Aufheben to Promote Druglikeness: Chemical Modification Strategies to Improve Aqueous Solubility and Permeability.Journal of medicinal chemistry · 2025Review
- Macrocyclic Peptides Containing an Imidazopyridinium (IPbioRxiv : the preprint server for biology · 2025Article
- Article
- Discovery of Cell-Permeable Macrocyclic Cyclin A/B RxL Inhibitors that Demonstrate Antitumor Activity.Journal of medicinal chemistry · 2025Article
- Systematic Determination of the Impact of Structural Edits on Peptide Accumulation into Mycobacteria.ACS chemical biology · 2025Article
- In-vitro Evaluation of p-Sulfonatocalix[n] arenes (SCnA) as Novel Excipients Using a Vectorized BCS Approach.AAPS PharmSciTech · 2025Article
- Peptide-Aware Chemical Language Model Successfully Predicts Membrane Diffusion of Cyclic Peptides.Journal of chemical information and modeling · 2025Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective, on-resin N-methylation of cyclic peptides to generate compounds with drug-like membrane permeability and oral bioavailability. The selectivity and degree of N-methylation of the cyclic peptide was dependent on backbone stereochemistry, suggesting that conformation dictates the regiochemistry of the N-methylation reaction. The permeabilities of the N-methyl variants were corroborated by computational studies on a 1,024-member virtual library of N-methyl cyclic peptides. One of the most permeable compounds, a cyclic hexapeptide (molecular mass = 755 Da) with three N-methyl groups, showed an oral bioavailability of 28% in rat.
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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.