Novel anti-HIV-1 activity produced by conjugating unsulfated dextran with polyl-lysine
| Autor: | Ken-ichi Tanamoto, Takahiro Ohtsuki, Hiroshi Ushijima, Hiroshi Akiyama, Hiroo Hoshino, Ariful Hoque, Atsushi Oue, Haruyo Mori, Fumie Kano, Nana Kawasaki, Hiromi Sakagami, Kosuke Nakamura, Haruko Ogawa |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Anti-HIV Agents viruses Lysine HIV Infections Virus Replication Peripheral blood mononuclear cell Virus Cell Line Mice chemistry.chemical_compound Sulfation Viral entry Virology Animals Humans Polylysine Pharmacology Mice Inbred BALB C biology Dextrans Virus Internalization Dextran chemistry Proteoglycan Biochemistry HIV-1 biology.protein Female Proteoglycans Conjugate |
| Zdroj: | Antiviral Research. 94:89-97 |
| ISSN: | 0166-3542 |
| Popis: | A conjugate of poly l -lysine (PLL) with unsulfated dextran produced by reductive amination was found to have remarkable anti-HIV-1 activity against both the macrophage-tropic R5 virus Ba-L and T-cell line tropic X4 virus IIIB strains, although neither PLL nor dextran has such activity. The conjugate is a pseudoproteoglycan (pseudoPG) that simulates the structure of a proteoglycan. Conjugation with dextran was found to produce an antiviral effect in three kinds of assay systems including a human CD4+ T-cell line, and the pseudoPG synthesized using 10 kDa PLL and 10 kDa dextran showed EC50 4–40 times lower than that of sulfated dextran or heparin against Ba-L and EC50 equal to that against IIIB, indicating that PLL–dextran (PLL–Dex) was more effective against R5 virus than sulfated polysaccharides. PLL–Dex significantly suppressed a clinically isolated R5 virus from primary peripheral blood mononuclear cells. PLL–Dex interacted with the virus during adsorption to the cell and also decreased virus entry into the cell, suggesting PLL–Dex has multiple preventive mechanisms against HIV-1. |
| Databáze: | OpenAIRE |
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