The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Conformational Flexibility, Internal Hydrogen Bonding, and Passive Membrane Permeability: Successful in Silico Prediction of the Relative Permeabilities of Cyclic Peptides
Abstract
We report an atomistic physical model for the passive membrane permeability of cyclic peptides. The computational modeling was performed in advance of the experiments and did not involve the use of "training data". The model explicitly treats the conformational flexibility of the peptides by extensive conformational sampling in low (membrane) and high (water) dielectric environments. The passive membrane permeabilities of 11 cyclic peptides were obtained experimentally using a parallel artificial membrane permeability assay (PAMPA) and showed a linear correlation with the computational results with R(2) = 0.96. In general, the results support the hypothesis, already well established in the literature, that the ability to form internal hydrogen bonds is critical for passive membrane permeability and can be the distinguishing factor among closely related compounds, such as those studied here. However, we have found that the number of internal hydrogen bonds that can form in the membrane and the solvent-exposed polar surface area correlate more poorly with PAMPA permeability than our model, which quantitatively estimates the solvation free energy losses upon moving from high-dielectric water to the low-dielectric interior of a membrane.
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Cites
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Molecular properties that influence the oral bioavailability of drug candidates
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The mechanism of action of cyclosporin A and FK506
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Permeability of small nonelectrolytes through lipid bilayer membranes
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The exploration of macrocycles for drug discovery — an underexploited structural class
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The Current State of Peptide Drug Discovery: Back to the Future?
Henninot, A., Collins, J. C., & Nuss, J. M. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00318 · Cited by 1,113
Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins
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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
Discovery of a Covalent Inhibitor of KRAS G12C (AMG 510) for the Treatment of Solid Tumors
Lanman, B. A., Allen, J. R., Allen, J. G., Amegadzie, A. K., Ashton, K. S., Booker, S. K., Chen, J. J., Chen, N., Frohn, M. J., Goodman, G., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01180 · Cited by 765
Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts
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Strategic Approaches to Optimizing Peptide ADME Properties
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Orally Absorbed Cyclic Peptides
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On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds
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., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.664 · Cited by 386
Self-citationCyclic peptide drugs approved in the last two decades (2001–2021)
Zhang, H., & Chen, S. (2022) · RSC Chemical Biology · doi:10.1039/d1cb00154j · Cited by 319
Permeability across lipid membranes
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Quantifying the chameleonic properties of macrocycles and other high-molecular-weight drugs
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Systemic delivery of peptides by the oral route: Formulation and medicinal chemistry approaches
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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
Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity
Klein, V. G., Bond, A. G., Craigon, C., Lokey, R. S., & Ciulli, A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01496 · Cited by 152
Self-citationBockus, A. T., Schwochert, J. A., Pye, C. R., Townsend, C. E., Sok, V., Bednarek, M. A., & Lokey, R. S. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00919 · Cited by 135
Self-citation
Metadata
- Authors
- Rezai, T., Bock, J. E., Zhou, M. V., Kalyanaraman, C., Lokey, R. S., & Jacobson, M. P.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-10-06
- Volume
- 128
- Issue
- 43
- Pages
- 14073-14080
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2136359146
- Cited by
- 416
- References
- 5
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
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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.
