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Biologically active oligodeoxyribonucleotides-IX. Synthesis and anti-HIV-1 activity of hexadeoxyribonucleotides, TGGGAG, bearing 3′- and 5′-end-modification |
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| Authors: | Makoto Koizumi Rika Koga Hitoshi Hotoda Kenji Momota Toshinori Ohmine Hidehiko Furukawa Toshinori Agatsuma Takashi Nishigaki Koji Abe Toshiyuki Kosaka Shinya Tsutsumi Junko Sone Masakatsu Kaneko Satoshi Kimura Kaoru Shimada |
| Institution: | a Exploratory Chemistry Research Laboratory, Sankyo Co., Ltd, Tokyo 140, Japan b Biological Research Laboratory, Sankyo Co., Ltd, Tokyo 140, Japan c Analytical and Metabolic Research Laboratory, Sankyo Co., Ltd, Tokyo 140, Japan d Department of Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108, Japan e Department of Infection Control and Prevention, the University of Tokyo Hospital, Tokyo 113, Japan f Tokyo Senbai Hospital, Tokyo 108, Japan |
| Abstract: | We have determined that hexadeoxyribonucleotides (5′TGGGAG3′), with modified aromatic groups such as a trityl group at the 5′-end, have anti-HIV-1 activity in vitro. The 6-mer bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5′-end had the most potent activity and the least cytotoxicity. When the 3′-end of the 5′-(3,4-DBB)-modified 6-mer was substituted with a 2-hydroxyethylphosphate, a 2-hydroxyethylthiophosphate, or a methylphosphate group at the 3′-end, anti-HIV-1 activity increased. Moreover, among various 3′- and 5′-end-modified 6-mers that were tested, the 6-mer (R-95288) bearing a 3,4-DBB group at the 5′-end and a 2-hydroxyethylphosphate group at the 3′-end was the most stable, when incubated with mouse, rat, or human plasma. Therefore, R-95288 was chosen as the best candidate for possible use in therapy on the basis of its anti-HIV-1 activity. |
| Keywords: | nuclease-resistance aptamer 3 4-dibenzyloxybenzyl 2-hydroxyethylphosphate quadruplex |
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