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Journal of Virology, February 1999, p. 1719-1723, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

T134, a Small-Molecule CXCR4 Inhibitor, Has No Cross-Drug Resistance with AMD3100, a CXCR4 Antagonist with a Different Structure

Rieko Arakaki,1 Hirokazu Tamamura,2 Mariappan Premanathan,1 Kenji Kanbara,1 Sivasundaram Ramanan,1 Katsura Mochizuki,3 Masanori Baba,4 Nobutaka Fujii,2 and Hideki Nakashima1,*

Department of Microbiology and Immunology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544,1 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501,2 Department of Chemistry, Faculty of Science and Graduate School of Integrated Science, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027,3 and Center for Chronic Viral Diseases, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520,4 Japan

Received 10 August 1998/Accepted 15 October 1998

T22, an analog of polyphemusin II (18 amino acid residues), was found to block T-tropic human immunodeficiency virus type 1 (HIV-1) entry into target cells as a CXCR4 inhibitor. We synthesized T134, a small analog (14 amino acid residues) of T22 with reduced positive charges. T134 exhibited highly potent activity and significantly less cytotoxicity in comparison to that of T22. T134 prevents the anti-CXCR4 monoclonal antibody from binding to peripheral blood mononuclear cells but has no effect on the binding of anti-CCR5 monoclonal antibodies. Since T134 inhibits the binding of stromal cell-derived factor-1 (SDF-1) to MT-4 cells, it seems that T134 prevents HIV-1 entry by binding to CXCR4. The bicyclam AMD3100 has also been shown to block HIV-1 entry via CXCR4 but not via CCR5. Both T134 and AMD3100 are CXCR4 antagonists and low-molecular-weight compounds but have different structures. Our results indicate that T134 is active against wild-type T-tropic HIV-1 strains and against AMD3100-resistant strains.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. Phone: 81-99-275-6150. Fax: 81-99-275-6158. E-mail: hidekin{at}dentb.hal.kagoshima-u.ac.jp.

Journal of Virology, February 1999, p. 1719-1723, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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