The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
ShK-Dap22, a Potent Kv1.3-specific Immunosuppressive Polypeptide
Open accessAbstract
The voltage-gated potassium channel in T lymphocytes, Kv1.3, is an important molecular target for immunosuppressive agents. A structurally defined polypeptide, ShK, from the sea anemone Stichodactyla helianthus inhibited Kv1.3 potently and also blocked Kv1.1, Kv1.4, and Kv1.6 at subnanomolar concentrations. Using mutant cycle analysis in conjunction with complementary mutagenesis of ShK and Kv1.3, and utilizing the structure of ShK, we determined a likely docking configuration for this peptide in the channel. Based upon this topological information, we replaced the critical Lys22 in ShK with the positively charged, non-natural amino acid diaminopropionic acid (ShK-Dap22) and generated a highly selective and potent blocker of the T-lymphocyte channel. ShK-Dap22, at subnanomolar concentrations, suppressed anti-CD3 induced human T-lymphocyte [3H]thymidine incorporation in vitro. Toxicity with this mutant peptide was low in a rodent model, with a median paralytic dose of approximately 200 mg/kg body weight following intravenous administration. The overall structure of ShK-Dap22 in solution, as determined from NMR data, is similar to that of native ShK toxin, but there are some differences in the residues involved in potassium channel binding. Based on these results, we propose that ShK-Dap22 or a structural analogue may have use as an immunosuppressant for the prevention of graft rejection and for the treatment of autoimmune diseases.
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The functional network of ion channels in T lymphocytes
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Up-regulation of the IKCa1 Potassium Channel during T-cell Activation
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Metadata
- Authors
- Kalman, K., Pennington, M. W., Lanigan, M. D., Nguyen, A., Rauer, H., Mahnir, V., Paschetto, K., Kem, W. R., Grissmer, S., Gutman, G. A., Christian, E. P., Cahalan, M. D., Norton, R. S., & Chandy, K. G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 273
- Issue
- 49
- Pages
- 32697-32707
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2118593499
- Cited by
- 256
- References
- 34
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: ShK-Dap22, a Potent Kv1.3-specific Immunosuppressive Polypeptide. https://app.cochat.ai/papers/10.1074/jbc.273.49.32697
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- Kalman, K., Pennington, M. W., Lanigan, M. D., Nguyen, A., Rauer, H., Mahnir, V., Paschetto, K., Kem, W. R., Grissmer, S., Gutman, G. A., Christian, E. P., Cahalan, M. D., Norton, R. S., & Chandy, K. G. (1998). ShK-Dap22, a Potent Kv1.3-specific Immunosuppressive Polypeptide. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.49.32697
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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.
