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 trans-activation 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 0.5 and 1 μM, 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.