The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Understanding Cell Penetration of Cyclic Peptides
Open accessAbstract
Approximately 75% of all disease-relevant human proteins, including those involved in intracellular protein-protein interactions (PPIs), are undruggable with the current drug modalities (i.e., small molecules and biologics). Macrocyclic peptides provide a potential solution to these undruggable targets because their larger sizes (relative to conventional small molecules) endow them the capability of binding to flat PPI interfaces with antibody-like affinity and specificity. Powerful combinatorial library technologies have been developed to routinely identify cyclic peptides as potent, specific inhibitors against proteins including PPI targets. However, with the exception of a very small set of sequences, the vast majority of cyclic peptides are impermeable to the cell membrane, preventing their application against intracellular targets. This Review examines common structural features that render most cyclic peptides membrane impermeable, as well as the unique features that allow the minority of sequences to enter the cell interior by passive diffusion, endocytosis/endosomal escape, or other mechanisms. We also present the current state of knowledge about the molecular mechanisms of cell penetration, the various strategies for designing cell-permeable, biologically active cyclic peptides against intracellular targets, and the assay methods available to quantify their cell-permeability.
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
Molecular properties that influence the oral bioavailability of drug candidates
Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020017n · Cited by 8,420
Therapeutic peptides: Historical perspectives, current development trends, and future directions
Lau, J. L., & Dunn, M. K. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.06.052 · Cited by 1,879
Wadia, J. S., Stan, R. V., & Dowdy, S. F. (2004) · Nature Medicine · doi:10.1038/nm996 · Cited by 1,647
Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L., & Korsmeyer, S. J. (2004) · Science · doi:10.1126/science.1099191 · Cited by 1,349
Kansy, M., Senner, F., & Gubernator, K. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm970530e · Cited by 1,304
Contemporary strategies for peptide macrocyclization
White, C. J., & Yudin, A. K. (2011) · Nature Chemistry · doi:10.1038/nchem.1062 · Cited by 1,088
The proton sponge: a trick to enter cells the viruses did not exploit
Behr, J.-P. (1997) · CHIMIA · doi:10.2533/chimia.1997.34 · Cited by 933
Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown
Wittrup, A., Ai, A., Liu, X., Hamar, P., Trifonova, R., Charisse, K., Manoharan, M., Kirchhausen, T., & Lieberman, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3298 · Cited by 693
Mechanism of oligonucleotide release from cationic liposomes.
Zelphati, O., & Szoka, F. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11493 · Cited by 634
Cited by
The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics
Qian, L., Lin, X., Gao, X., Khan, R. U., Liao, J.-Y., Du, S., Ge, J., Zeng, S., & Yao, S. Q. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00915 · Cited by 155
GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf
Zhang, Z., Gao, R., Hu, Q., Peacock, H., Peacock, D. M., Dai, S., Shokat, K. M., & Suga, H. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00514 · Cited by 124
Protease-Resistant Peptides for Targeting and Intracellular Delivery of Therapeutics
Lucana, M. C., Arruga, Y., Petrachi, E., Roig, A., Lucchi, R., & Oller-Salvia, B. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122065 · Cited by 102
Drug‐Like Properties in Macrocycles above MW 1000: Backbone Rigidity versus Side‐Chain Lipophilicity
Furukawa, A., Schwochert, J., Pye, C. R., Asano, D., Edmondson, Q. D., Turmon, A. C., Klein, V. G., Ono, S., Okada, O., & Lokey, R. S. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202004550 · Cited by 79
Liao, H.-J., & Tzen, J. T. C. (2022) · Metabolites · doi:10.3390/metabo12060549 · Cited by 21
Metadata
- Authors
- Dougherty, P. G., Sahni, A., & Pei, D.
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-05-14
- Volume
- 119
- Issue
- 17
- Pages
- 10241-10287
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- OpenAlex
- W2945543430
- Cited by
- 570
- References
- 18
- FWCI
- 3.95
- 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: Understanding Cell Penetration of Cyclic Peptides. https://app.cochat.ai/papers/10.1021/acs.chemrev.9b00008
- The paper
- Dougherty, P. G., Sahni, A., & Pei, D. (2019). Understanding Cell Penetration of Cyclic Peptides. Chemical Reviews. https://doi.org/10.1021/acs.chemrev.9b00008
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.
