title: Anti-HIV-1 activity and mode of action of mirror image oligodeoxynucleotide analogue of Zintevir.
abstract: Zintevir is an oligonucleotide analogue, which has the phosphorothioate modification at both termini, that forms a K(+)-induced quadruplex structure and shows potent anti-human immunodeficiency virus (HIV)-1 activity. We synthesized the non-modified analogue (D-17mer) of Zintevir and its enantiomer (L-17mer), and compared their anti-HIV-1 activity and molecular mechanism of action. Although L-17mer forms the exact mirror image quadruplex structure of D-17mer, which has a very similar structure with Zintevir, L-17mer showed comparable anti-HIV-1 activity with Zintevir. The results obtained by the time-of-addition experiments and the immunofluorescence binding assay strongly suggest that the primary molecular target of L-17mer is the viral gp120 envelope protein as well as Zintevir, regardless of their reciprocal chirality.
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. urata@gly.oups.ac.jp
authors.forename: Hidehito
authors.initials: H
authors.lastname: Urata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kumashiro
authors.forename: Takuya
authors.initials: T
authors.lastname: Kawahata
authors.forename: Toru
authors.initials: T
authors.lastname: Otake
authors.forename: Masao
authors.initials: M
authors.lastname: Akagi
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D002461:Cell Line, Transformed; D002942:Circular Dichroism; D004355:Drug Stability; D005434:Flow Cytometry; D015750:Genes, gag / Q000187:drug effects / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D043264:Phosphodiesterase I / Q000378:metabolism; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013237:Stereoisomerism; D013696:Temperature; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D009841:Oligonucleotides; C098172:T 30177; D015719:Single-Strand Specific DNA and RNA Endonucleases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom