The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Testing the Conformational Hypothesis of Passive Membrane Permeability Using Synthetic Cyclic Peptide Diastereomers
Abstract
Little is known about the effect of conformation on passive membrane diffusion rates in small molecules. Evidence suggests that intramolecular hydrogen bonding may play a role by reducing the energetic cost of desolvating hydrogen bond donors, especially amide N-H groups. We set out to test this hypothesis by investigating the passive membrane diffusion characteristics of a series of cyclic peptide diastereomers based on the sequence cyclo[Leu-Leu-Leu-Leu-Pro-Tyr]. We identified two cyclic hexapeptide diastereomers based on this sequence, whose membrane diffusion rates differed by nearly two log units. Results of solution NMR studies and hydrogen/deuterium (H/D) exchange experiments showed that membrane diffusion rates correlated with the degree of intramolecular hydrogen bonding and H/D exchange rates. The most permeable diastereomer, cyclo[d-Leu-d-Leu-Leu-d-Leu-Pro-Tyr] (1), exhibited a passive membrane diffusion rate comparable to that of the orally available drug cyclosporine A.
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
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139
The mechanism of action of cyclosporin A and FK506
Schreiber, S. L., & Crabtree, G. R. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90111-j · Cited by 2,127
Kansy, M., Senner, F., & Gubernator, K. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970530e · Cited by 1,304
Hruby, V. J., al-Obeidi, F., & Kazmierski, W. (1990) · Biochemical Journal · doi:10.1042/bj2680249 · Cited by 518
Conformation of β-hairpins in protein structures
Sibanda, B. L., Blundell, T. L., & Thornton, J. M. (1989) · Journal of Molecular Biology · doi:10.1016/0022-2836(89)90583-4 · Cited by 474
The Influence of Peptide Structure on Transport Across Caco-2 Cells
Conradi, R. A., Hilgers, A. R., Ho, N. F. H., & Burton, P. S. (1991) · Pharmaceutical Research · doi:10.1023/a:1015825912542 · Cited by 228
PAMPA—a drug absorption in vitro model
Bermejo, M., Avdeef, A., Ruiz, A., Nalda, R., Ruell, J. A., Tsinman, O., González, I., Fernández, C., Sánchez, G., Garrigues, T. M., et al. (2004) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2003.10.009 · Cited by 206
How Structural Features Influence the Biomembrane Permeability of Peptides
Burton, P. S., Conradi, R. A., Ho, N. F. H., Hilgers, A. R., & Borchardt, R. T. (1996) · Journal of Pharmaceutical Sciences · doi:10.1021/js960067d · Cited by 176
The Effect of β-Turn Structure on the Passive Diffusion of Peptides Across Caco-2 Cell Monolayers
Knipp, G. T., VanderVelde, D. G., Siahaan, T. J., et al. (1997) · Pharmaceutical Research · doi:10.1023/a:1012152117703 · Cited by 82
Koehorst, R. B. M., Spruijt, R. B., Vergeldt, F. J., & Hemminga, M. A. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.043208 · Cited by 76
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
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
Orally Absorbed Cyclic Peptides
Nielsen, D. S., Shepherd, N. E., Xu, W., Lucke, A. J., Stoermer, M. J., & Fairlie, D. P. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00838 · Cited by 445
Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics
Ding, Y., Ting, J. P., Liu, J., Al-Azzam, S., Pandya, P., & Afshar, S. (2020) · Amino Acids · doi:10.1007/s00726-020-02890-9 · Cited by 200
Metadata
- Authors
- Rezai, T., Yu, B., Millhauser, G. L., Jacobson, M. P., & Lokey, R. S.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-02-04
- Volume
- 128
- Issue
- 8
- Pages
- 2510-2511
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2045093121
- Cited by
- 490
- References
- 11
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- closed
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: Testing the Conformational Hypothesis of Passive Membrane Permeability Using Synthetic Cyclic Peptide Diastereomers. https://app.cochat.ai/papers/10.1021/ja0563455
- The paper
- Rezai, T., Yu, B., Millhauser, G. L., Jacobson, M. P., & Lokey, R. S. (2006). Testing the Conformational Hypothesis of Passive Membrane Permeability Using Synthetic Cyclic Peptide Diastereomers. Journal of the American Chemical Society. https://doi.org/10.1021/ja0563455
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.
