Design of beta-hairpin peptidomimetics that inhibit binding of alpha-helical HIV-1 Rev protein to the rev response element RNA.

Abstract

The virally encoded Rev protein of human immunodeficiency virus type-1 (HIV-1) plays a critical role in viral replication by regulating the transport of unspliced and partially spliced viral RNA from the nucleus to the cytoplasm of infected cells.[1, 2] Rev binds first to a specific region of the HIV-1 mRNA, called the Rev responsive element (RRE) of stem loop IIb (Figure 1); subsequent to this initial binding event, approximately 10 additional Rev molecules oligomerize through protein–protein and protein–RNA interactions and coat the entire RRE.[3] Because of its essential role in viral replication, the interaction between Rev protein and the high-affinity RRE binding site represents an attractive yet unexploited target for antiviral therapy.