Targeting RNA with peptidomimetic oligomers in human cells.
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. Here we report that two TAR RNA-binding peptidomimetics, oligourea and oligocarbamate, inhibit transcriptional activation by Tat protein in human cells with an IC50 of approximately 0.5 and 1 microM, respectively. Peptidomimetics that can target specific RNA structures provide novel molecules that can be used to control cellular processes involving protein-RNA interactions in vivo.
Department of Pharmacology, Robert Wood Johnson Medical School, and Molecular Biosciences Graduate Program at Rutgers State University, Piscataway, NJ 08854, USA.
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Tamilarasu
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Huq
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Rana
D002219:Carbamates / Q000494:pharmacology; D015696:Gene Products, tat / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D011108:Polymers / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D014508:Urea / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D002219:Carbamates; D015696:Gene Products, tat; D011108:Polymers; D054322:tat Gene Products, Human Immunodeficiency Virus; D012313:RNA; D014508:Urea