Design, synthesis, and biological activity of a cyclic peptide: an inhibitor of HIV-1 tat-TAR interactions 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. 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.