title: Interaction of new PNA-based molecules with TAR RNA of HIV-1: molecular modelling and biological evaluation.
abstract: During the HIV-1 replication process, interactions between the RNA sequence, named TAR RNA, and the viral protein, Tat, permit a fast and efficient transcription of viral DNA into RNA. Based on the NMR structure of TAR RNA from the PDB, two Peptidic Nucleic Analog- (PNA) based molecules were designed by molecular modelling, the first one targeting G32 U31 and the second targeting U31 C30 free loop bases. Before designing the molecules, the flexibility of the TAR RNA was evaluated by molecular dynamics (MD). The molecules studied are composed of three domains: an arginine, a linker, and two PNA bases. First, molecules were designed and the linker length was optimized to fit the TAR RNA; second, a MD simulation on the TAR RNA molecule complex was performed to validate the molecular structure. Optimal molecules were synthesized and tested on infected cells. The experimental results support the choices made in the design of the molecules.
authors.affiliation: Laboratoire Arômes, Synthèses et Interactions, Equipe Chimiométrie et Modélisation, Université de Nice Sophia-Antipolis, F 06108 Nice, France.
authors.forename: R
authors.initials: R
authors.lastname: Terreux
authors.forename: S
authors.initials: S
authors.lastname: Pairot
authors.forename: D
authors.initials: D
authors.lastname: Cabrol-Bass
authors.forename: N
authors.initials: N
authors.lastname: Patino
authors.forename: R
authors.initials: R
authors.lastname: Condom
mesh_terms: D002942:Circular Dichroism; D003198:Computer Simulation; D015696:Gene Products, tat / Q000737:chemistry*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000737:chemistry; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000737:chemistry*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015696:Gene Products, tat; D009757:Nylons; D020135:Peptide Nucleic Acids; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus