title: Novel anti-HIV-1 activity produced by conjugating unsulfated dextran with polyL-lysine.
abstract: A conjugate of polyL-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 EC(50) 4-40 times lower than that of sulfated dextran or heparin against Ba-L and EC(50) 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.
authors.affiliation: Graduate School of Humanities and Sciences and The Glycoscience Institute, Ochanomizu University, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ohtsuki
authors.forename: Haruyo
authors.initials: H
authors.lastname: Mori
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hoshino
authors.forename: Ariful
authors.initials: A
authors.lastname: Hoque
authors.forename: Atsushi
authors.initials: A
authors.lastname: Oue
authors.forename: Fumie
authors.initials: F
authors.lastname: Kano
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tanamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ushijima
authors.forename: Nana
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akiyama
authors.forename: Haruko
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011107:Polylysine / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000737:chemistry / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D003911:Dextrans; D011509:Proteoglycans; D011107:Polylysine