Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides.
Chitooligosaccharides are nontoxic and water-soluble compounds obtained by enzymatic degradation of chitosan, which is derived from chitin by a deacetylation process. Chitooligosaccharides possess broad range of activities such as antitumour, antifungal, antibacterial activities. Sulfated chitooligosaccharides (SCOSs) with different molecular weights were synthesized by a random sulfation reaction. In the present study, anti-HIV-1 properties of SCOSs and the impact of molecular weight on their inhibitory activity were investigated. SCOS III (MW 3-5 kDa) was found to be the most effective compound to inhibit HIV-1 replication. At nontoxic concentrations, SCOS III exhibited remarkable inhibitory activities on HIV-1-induced syncytia formation (EC(50) 2.19 microg/ml), lytic effect (EC(50) 1.43 microg/ml), and p24 antigen production (EC(50) 4.33 microg/ml and 7.76 microg/ml for HIV-1(RF) and HIV-1(Ba-L), respectively). In contrast, unsulfated chitooligosaccharides showed no activity against HIV-1. Furthermore, it was found that SCOS III blocked viral entry and virus-cell fusion probably via disrupting the binding of HIV-1 gp120 to CD4 cell surface receptor. These results suggest that sulfated chitooligosaccharides represent novel candidates for the development of anti-HIV-1 agent.
Artan
Murat
M
Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.
Karadeniz
Fatih
F
Karagozlu
Mustafa Zafer
MZ
Kim
Moon-Moo
MM
Kim
Se-Kwon
SK
D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D013464:Sulfuric Acids / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D009844:Oligosaccharides; D013464:Sulfuric Acids; D008156:Luciferases