Structure-based design of an RNA-binding p-terphenylene scaffold that inhibits HIV-1 rev protein function

Abstract

Rev(ersing) RNA binding: RNA-binding inhibitors based on a bilaterally substituted p-terphenylene scaffold (green) project their substituents in a broad spatial angle and reproduce the interactions of a protein α-helix (red) embedded in its RNA receptor. These terphenyls can mimic one α-helix of the HIV-1 protein Rev and inhibit Rev function and HIV-1 replication in cells. This scaffold may open new avenues for targeting nucleic acids with small molecules. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.