title: Artificial nucleobase-amino acid conjugates: a new class of TAR RNA binding agents.
abstract: The human immunodeficiency virus type-1 (HIV-1) Tat protein stimulates transcriptional elongation. Tat is involved in the transcription machinery by binding to the transactivation response region (TAR) RNA stem-loop structure, which is encoded by the 5' leader sequence found in all HIV-1 mRNAs. Herein, we report the rational design, synthesis, and in vitro evaluation of new RNA binding agents that were conceived in order to bind strongly and selectively to the stem-loop structure of TAR RNA and, thus, inhibit the Tat/TAR interaction. We have demonstrated that the conjugation of modified nucleobases, able to interact specifically with an RNA base pair, and various amino acids allows these motifs to bind the target RNA selectively and in a cooperative manner that leads to the inhibition of viral replication in HIV-infected cells.
authors.affiliation: Institut de Chimie de Nice UMR7272 CNRS, Université de Nice Sophia Antipolis, Parc Valrose, 06108 Nice cedex 1 (France), Fax: (+33) 4-92076151.
authors.forename: Jean-Patrick
authors.initials: JP
authors.lastname: Joly
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mata
authors.forename: Patrick
authors.initials: P
authors.lastname: Eldin
authors.forename: Laurence
authors.initials: L
authors.lastname: Briant
authors.forename: Fabien
authors.initials: F
authors.lastname: Fontaine-Vive
authors.forename: Maria
authors.initials: M
authors.lastname: Duca
authors.forename: Rachid
authors.initials: R
authors.lastname: Benhida
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D015696:Gene Products, tat / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011687:Purines / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000596:Amino Acids; D019380:Anti-HIV Agents; D015696:Gene Products, tat; D011687:Purines; D011743:Pyrimidines; D012313:RNA
keywords: RNA recognition; amino acids; antiviral agents; cooperative binding; nucleobases