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A Small Molecule CXCR4 Inhibitor that Blocks T Cell Line–tropic HIV-1 Infection
Open accessAbstract
Several members of the chemokine receptor family have been shown to function in association with CD4 to permit human immunodeficiency virus type 1 (HIV-1) entry and infection. The CXC chemokine receptor CXCR4/fusin is a receptor for pre–B cell growth stimulating factor (PBSF)/stromal cell–derived factor 1 (SDF-1) and serves as a coreceptor for the entry of T cell line–tropic HIV-1 strains. Thus, the development of CXCR4 antagonists or agonists may be useful in the treatment of HIV-1 infection. T22 ([Tyr5,12,Lys7]-polyphemusin II) is a synthesized peptide that consists of 18 amino acid residues and an analogue of polyphemusin II isolated from the hemocyte debris of American horseshoe crabs (Limulus polyphemus). T22 was found to specifically inhibit the ability of T cell line–tropic HIV-1 to induce cell fusion and infect the cell lines transfected with CXCR4 and CD4 or peripheral blood mononuclear cells. In addition, T22 inhibited Ca2+ mobilization induced by pre–B cell growth stimulating factor (PBSF)/SDF-1 stimulation through CXCR4. Thus, T22 is a small molecule CXCR4 inhibitor that blocks T cell line–tropic HIV-1 entry into target cells.
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Citations
Cited by
Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease
Berger, E. A., Murphy, P. M., & Farber, J. M. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.657 · Cited by 2,180
International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors
Murphy, P. M., Baggiolini, M., Charo, I. F., Hébert, C. A., Horuk, R., Matsushima, K., Miller, L. H., Oppenheim, J. J., & Power, C. A. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01439-x · Cited by 1,817
Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection
De Clercq, E. (2000) · Medicinal Research Reviews · doi:10.1002/1098-1128(200009)20:5<323::aid-med1>3.0.co;2-a · Cited by 355
Tamamura, H., Hori, A., Kanzaki, N., Hiramatsu, K., Mizumoto, M., Nakashima, H., Yamamoto, N., Otaka, A., & Fujii, N. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00824-x · Cited by 285
Self-citationBroxmeyer, H. E., Kohli, L., Kim, C. H., Lee, Y., Mantel, C., Cooper, S., Hangoc, G., Shaheen, M., Li, X., & Clapp, D. W. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.1002495 · Cited by 162
Metadata
- Authors
- Murakami, T., Nakajima, T., Koyanagi, Y., Tachibana, K., Fujii, N., Tamamura, H., Yoshida, N., Waki, M., Matsumoto, A., Yoshie, O., Kishimoto, T., Yamamoto, N., & Nagasawa, T.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1997-10-20
- Volume
- 186
- Issue
- 8
- Pages
- 1389-1393
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2150898533
- Cited by
- 398
- References
- 0
- FWCI
- 17.04
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Murakami, T., Nakajima, T., Koyanagi, Y., Tachibana, K., Fujii, N., Tamamura, H., Yoshida, N., Waki, M., Matsumoto, A., Yoshie, O., Kishimoto, T., Yamamoto, N., & Nagasawa, T. (1997). A Small Molecule CXCR4 Inhibitor that Blocks T Cell Line–tropic HIV-1 Infection. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.186.8.1389
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