The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds
Open accessAbstract
Backbone N-methylation is common among peptide natural products and has a significant 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 determined by 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 1024-member virtual library of N-methyl cyclic peptides. One of the most permeable compounds, a cyclic hexapeptide (MW = 755) with three N-methyl groups, showed an oral bioavailability of 28% in rat.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Kansy, M., Senner, F., & Gubernator, K. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970530e · Cited by 1,304
Cited by
Macrocyclic Peptides as Drug Candidates: Recent Progress and Remaining Challenges
Vinogradov, A. A., Yin, Y., & Suga, H. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b13178 · Cited by 848
Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins
Yang, N. J., & Hinner, M. J. (2015) · Methods in Molecular Biology · doi:10.1007/978-1-4939-2272-7_3 · Cited by 826
Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates
Doak, B. C., Over, B., Giordanetto, F., & Kihlberg, J. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.08.013 · Cited by 835
Strategic Approaches to Optimizing Peptide ADME Properties
Di, L. (2015) · The AAPS Journal · doi:10.1208/s12248-014-9687-3 · Cited by 669
N‐Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions
Chatterjee, J., Rechenmacher, F., & Kessler, H. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201205674 · Cited by 494
Metadata
- Authors
- White, T. R., Renzelman, C. M., Rand, A. C., Rezai, T., McEwen, C. M., Gelev, V. M., Turner, R. A., Linington, R. G., Leung, S. S. F., Kalgutkar, A. S., Bauman, J. N., Zhang, Y., Liras, S., Price, D. A., Mathiowetz, A. M., Jacobson, M. P., & Lokey, R. S.
- Venue
- Nature Chemical Biology
- Published
- 2011-09-25
- Volume
- 7
- Issue
- 11
- Pages
- 810-817
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2050991123
- Cited by
- 386
- References
- 1
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds. https://app.cochat.ai/papers/10.1038/nchembio.664
- The paper
- White, T. R., Renzelman, C. M., Rand, A. C., Rezai, T., McEwen, C. M., Gelev, V. M., Turner, R. A., Linington, R. G., Leung, S. S. F., Kalgutkar, A. S., Bauman, J. N., Zhang, Y., Liras, S., Price, D. A., Mathiowetz, A. M., Jacobson, M. P., & Lokey, R. S. (2011). On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds. Nature Chemical Biology. https://doi.org/10.1038/nchembio.664
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
