DNA aptamers as potential anti-HIV agents.
Guanine (G)-rich DNA sequences can adopt stable G-quadruplex structures by G-tetrad hydrogen-bonding and hydrophobic stacking. Recently, it has been shown that a DNA sequence forms an aptamer (termed 93del) and adopts a novel dimeric quadruplex folding topology in K+ solution. This aptamer exhibits anti-HIV1 integrase activity in the nanomolar range in vitro. A docking-based model of the 93del-integrase complex positions the DNA aptamer within a channel of the tetrameric integrase. This mutual fitting blocks several catalytic amino acid residues that are essential for integrase function, and accounts for the anti-HIV1 activity of the 93del aptamer.
Chou
Shan-Ho
SH
Institute of Biochemistry, National Chung-Hsing University, Taichung, Taiwan, Republic of China. shchou@nchu.edu.tw
Chin
Ko-Hsin
KH
Wang
Andrew H-J
AH
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism
D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D009841:Oligonucleotides; D004247:DNA