title: Pseudo--half-knot formation with RNA.
abstract: A pseudo--half-knot can be formed by binding an oligonucleotide asymmetrically to an RNA hairpin loop. This binding motif was used to target the human immunodeficiency virus TAR element, an important viral RNA structure that is the receptor for Tat, the major viral transactivator protein. Oligonucleotides complementary to different halves of the TAR structure bound with greater affinity than molecules designed to bind symmetrically around the hairpin. The pseudo--half-knot--forming oligonucleotides altered the TAR structure so that specific recognition and binding of a Tat-derived peptide was disrupted. This general binding motif may be used to disrupt the structure of regulatory RNA hairpins.
authors.affiliation: ISIS Pharmaceuticals, Carlsbad, CA 92008.
authors.forename: D J
authors.initials: DJ
authors.lastname: Ecker
authors.forename: T A
authors.initials: TA
authors.lastname: Vickers
authors.forename: T W
authors.initials: TW
authors.lastname: Bruice
authors.forename: S M
authors.initials: SM
authors.lastname: Freier
authors.forename: R D
authors.initials: RD
authors.lastname: Jenison
authors.forename: M
authors.initials: M
authors.lastname: Manoharan
authors.forename: M
authors.initials: M
authors.lastname: Zounes
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004279:DNA, Viral / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D006678:HIV / Q000235:genetics*; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D004279:DNA, Viral; D015696:Gene Products, tat; D009843:Oligoribonucleotides; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus