Bioisostere of valtrate, anti-HIV principle by inhibition for nuclear export of Rev

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 7, 2010, Pages 2159-2162

  Tamura, Satoru ^a   Shimizu, Nobuhiro ^b   Fujiwara, Katsuaki ^a   Kaneko, Masafumi ^b   Kimura, Tominori ^c,d   Murakami, Nobutoshi ^a,b  

^a OSAKA UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c RITSUMEIKAN UNIVERSITY   (Japan)

^d KANSAI MEDICAL UNIVERSITY   (Japan)

Author keywords

Anti HIV; Bioisostere; Iridoid; Rev export inhibitor; Valtrate

Indexed keywords

5,6 DIHYDROVALTRATE; ANTIVIRUS AGENT; BIOISOSTERE OF VALTRATE; HYDROXYL GROUP; REV PROTEIN; UNCLASSIFIED DRUG; VALTRATE;

ANTIVIRAL ACTIVITY; ARTICLE; DIELS ALDER REACTION; DRUG INHIBITION; DRUG MECHANISM; DRUG POTENCY; DRUG SYNTHESIS; EPOXIDATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; NUCLEAR EXPORT SIGNAL; STEREOCHEMISTRY;

ACTIVE TRANSPORT, CELL NUCLEUS; ANTI-HIV AGENTS; GENE PRODUCTS, REV; HELA CELLS; HIV INFECTIONS; HUMANS; IRIDOIDS; MOLECULAR CONFORMATION;

ALNUS;

EID: 77949487321     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.02.038     Document Type: Article

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12. 2 for 24 h. Transfection of pCG-HA-Rev (plasmid encoding HA-tagged Rev protein) and pCRRE/ΔRev (plasmid encoding Gag protein) plasmids into HeLa cells were performed using PolyFect® transfection reagent kit (QIAGEN) for 16 h according to the manufacturer's instructions. After the cells were washed, each solution of tested sample at an appropriate concentration in the medium containing 1% DMSO was inoculated and the whole was incubated at 37 °C for further 12 h. Cells were rinsed with cold D-PBS (-) twice and fixed with 4% formaldehyde/D-PBS (-) for 20 min. Then the cells were defatted with MeOH under shaking for 10 min and washed with cold D-PBS (-) thrice. After treatment with 10% FBS in Dulbecco's MEM medium for 30 min, the samples were incubated with anti-HA antibody (Roche) for 45 min followed by incubation with FITC-labeled anti-mouse IgG antibody (Vector) for 45 min. Localization of the HA-tagged Rev protein in the cells was examined under a fluorescence microscope, then image analysis was conducted by Scion image software (Scion) to determine Rev-export inhibitory activity. In the depicted pictures, several cells free from transfection displayed disperse weak fluorescence due to nonspecific binding of the antibodies.