title: Evaluation of mismatch-binding ligands as inhibitors for Rev-RRE interaction.
abstract: Drugs targeting the stem-loop IIB of Rev responsible element (RRE) of HIV-1 mRNA are potential therapeutic agents for HIV-1 infection. The stem loop is characterized by an internal loop consist of consecutive G-G and G-A mismatches, which is the single binding site for Rev protein for nuclear export of viral mRNA. We report here that ligands binding to G-G and G-A mismatches in duplex DNA also bind to the internal loop in competition with Rev peptide and lead to the dissociation of pre-formed Rev-RRE complex in a model system.
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Kyoto 615-8510, Japan. nakatani@sanken.osaka-u.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakatani
authors.forename: Souta
authors.initials: S
authors.lastname: Horie
authors.forename: Yuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Akio
authors.initials: A
authors.lastname: Kobori
authors.forename: Shinya
authors.initials: S
authors.lastname: Hagihara
mesh_terms: D020137:Base Pair Mismatch; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005454:Fluorescence Polarization; D015694:Gene Products, rev / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015752:Genes, env / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D008024:Ligands; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D009690:Nucleic Acid Conformation; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000187:drug effects*; D020349:Surface Plasmon Resonance; D013997:Time Factors; D054321:rev Gene Products, Human Immunodeficiency Virus
chemical_list: D015694:Gene Products, rev; D008024:Ligands; D009287:Naphthyridines; D011073:Polyamines; D015363:Quinolones; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus; D004247:DNA