title: RNA as a target for drug design, the example of Tat-TAR interaction.
abstract: One of the new targets in the battle against HIV-1 infection is the interaction between the viral transactivator and the transactivation response (TAR) element, which is necessary for HIV-1 replication. After an overview of the most recent structural studies of the Tat-TAR system, new TAR-targeted inhibitors are presented in several classes: antisense oligonucleotides, cationic peptides, intercalators and a large class of small RNA binding molecules. The method of library screening of RNA binding ligands in the search for new inhibitors is explained in detail. Inhibition of Tat-TAR interaction is considered as a realistic approach to develop new anti-HIV compounds. The RNA binding molecules in this review also demonstrate that the development of drugs that target RNA will become a feasible goal and that such compounds will be added in the future to the therapeutic arsenal to combat several diseases.
authors.affiliation: Laboratory of Medicinal Chemistry, Catholic University Leuven, Rega Institute, Minderbroedersstraat 10, Leuven, 3000, Belgium. piet.herdewijn@rega.kuleuven.ac.be
authors.forename: M
authors.initials: M
authors.lastname: Froeyen
authors.forename: P
authors.initials: P
authors.lastname: Herdewijn
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D015195:Drug Design; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D007364:Intercalating Agents; D016376:Oligonucleotides, Antisense; D010455:Peptides; D012367:RNA, Viral