title: Design, synthesis, and biological activity of a cyclic peptide: an inhibitor of HIV-1 tat-TAR interactions in human cells.
abstract: Replication of human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the transactivation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all HIV mRNAs. A number of cyclic peptides are known to possess antibiotic activity and increased biological stability. Here we report the design, synthesis, and biological activity of a cyclic peptide (2), which inhibits transcriptional activation by Tat protein in human cells with an IC50 of approximately 40 nM. Cyclic peptides that can target specific RNA structures provide a new class of small molecules that can be used to control cellular processes involving RNA-protein interactions in vivo.
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, and Molecular Biosciences Graduate Program at Rutgers State University, Piscataway, NJ 08854, USA.
authors.forename: N
authors.initials: N
authors.lastname: Tamilarasu
authors.forename: I
authors.initials: I
authors.lastname: Huq
authors.forename: T M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D015195:Drug Design; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D015696:Gene Products, tat / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D012367:RNA, Viral / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D019380:Anti-HIV Agents; D015696:Gene Products, tat; D008024:Ligands; D010456:Peptides, Cyclic; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus