ArticleNature communications2023
An amide to thioamide substitution improves the permeability and bioavailability of macrocyclic 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 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Stabilized thioamide peptide agonists of the neuropeptide Y type 2 receptor for targeted cancer imaging.RSC chemical biology · 2026Article
- Thioimidate Protection Enables Amide, Thioamide, and Amidine Installation at Aspartic Acid Residues.The Journal of organic chemistry · 2026Article
- Synthesis of Primary Thioamides by the Insertion of CSOrganic letters · 2026Article
- The Effect of Aza-Glycine Substitution on the Internalization of Dabcyl-Containing Short Oligoarginine.Biomedicines · 2026Article
- A Versatile Strategy for Head-to-Tail Macrocyclization and Traceless Backbone Editing of Short Peptides.Journal of the American Chemical Society · 2026Article
- Linker Engineering in Stapled Peptides for Enhanced Membrane Permeability: Screening and Optimization Strategies.International journal of molecular sciences · 2026Review
- Programmable Helicity and Macrocycle Symmetry in β-Peptides via Site-Selective Thioamide Substitution.Journal of the American Chemical Society · 2025Article
- C2PO: an ML-powered optimizer of the membrane permeability of cyclic peptides through chemical modification.Journal of cheminformatics · 2025Article
- Overcoming Oral Cavity Barriers for Peptide Delivery Using Advanced Pharmaceutical Techniques and Nano-Formulation Platforms.Biomedicines · 2025Review
- Thioamides in C5 Hydrogen Bonds: Implications for Protein β-Strands.The Journal of organic chemistry · 2025Article
- Unexpected Reactivity of Nitrones: Catalytic Insertion of CSOrganic letters · 2025Article
- End-to-End Backbone Cyclization Enhances Passive Permeability of bRo5 Oligomeric Depsipeptides with Nonlinear Size Dependence.ACS medicinal chemistry letters · 2025Article
- Design, synthesis, anti-inflammatory evaluation, and molecular docking studies of novel quinazoline-4(3RSC advances · 2025Article
- Unlocking the potential of the thioamide group in drug design and development.Future medicinal chemistry · 2025Article
- Selection of Nucleotide-Encoded Mass Libraries of Macrocyclic Peptides for Inaccessible Drug Targets.Chemical reviews · 2024Review
- Thioamides in medicinal chemistry and as small molecule therapeutic agents.European journal of medicinal chemistry · 2024Review
- Complementary Strategies for Installation of Thioimidates into Peptide Backbones.The Journal of organic chemistry · 2024Article
- CycPeptMP: enhancing membrane permeability prediction of cyclic peptides with multi-level molecular features and data augmentation.Briefings in bioinformatics · 2024Article
- Peptide and Peptidomimetic Inhibitors Targeting the Interaction of Collapsin Response Mediator Protein 2 with the N-Type Calcium Channel for Pain Relief.ACS pharmacology & translational science · 2024Review
- Influence of Aza-Glycine Substitution on the Internalization of Penetratin.Pharmaceutics · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Solvent shielding of the amide hydrogen bond donor (NH groups) through chemical modification or conformational control has been successfully utilized to impart membrane permeability to macrocyclic peptides. We demonstrate that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor (>C = O) through a thioamide substitution (>C = S). The membrane permeability is a consequence of the lower desolvation penalty of the macrocycle resulting from a concerted effect of conformational restriction, local desolvation of the thioamide bond, and solvent shielding of the amide NH groups. The enhanced permeability and metabolic stability on thioamidation improve the bioavailability of a macrocyclic peptide composed of hydrophobic amino acids when administered through the oral route in rats. Thioamidation of a bioactive macrocyclic peptide composed of polar amino acids results in analogs with longer duration of action in rats when delivered subcutaneously. These results highlight the potential of O to S substitution as a stable backbone modification in improving the pharmacological properties of peptide macrocycles.
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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.