Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by modification with oligomannose.
| Autor: | Cheng S; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou district, Beijing, 101408, China., Xu M; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou district, Beijing, 101408, China., Li M; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou district, Beijing, 101408, China., Feng Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou district, Beijing, 101408, China., He L; National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China., Liu T; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou district, Beijing, 101408, China., Ma L; National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. Electronic address: mal@chinaaids.cn., Li X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing, 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Huairou district, Beijing, 101408, China. Electronic address: lixb@im.ac.cn. |
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| Jazyk: | angličtina |
| Zdroj: | European journal of medicinal chemistry [Eur J Med Chem] 2024 Apr 05; Vol. 269, pp. 116299. Date of Electronic Publication: 2024 Mar 08. |
| DOI: | 10.1016/j.ejmech.2024.116299 |
| Abstrakt: | Dendritic cells (DCs) play a pivotal role in controlling HIV-1 infections of CD4 + T cells. DC-SIGN, which is expressed on the surface of DCs, efficiently captures HIV-1 virions by binding to the highly mannosylated membrane protein, gp120, and then the DCs transport the virus to target T cells in lymphoid organs. This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, by conjugation of the N-terminus with varying sizes of oligomannose, which are DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. Mechanistic studies indicated the dual-target binding of the conjugates. Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in increased inhibition of the viral infection of TZM-b1 cells (EC Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier Masson SAS. All rights reserved.) |
| Databáze: | MEDLINE |
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