Helical cyclic pentapeptides constrain HIV-1 Rev peptide for enhanced RNA binding
HIV-1 Rev is a 116 residue transporter protein that enters the host cell nucleus and uses its 17 amino acid segment (Rev34-50) to bind and capture a specific piece of RNA, the Rev Response Element (RRE), for transport to the cytoplasm. This is critical for HIV replication. In isolation, Rev34-50 shows negligible structure in water, but is alpha helical in a mixture of water and 2,2,2-trifluoroethanol (TFE) or when bound to RRE. Here we report that helix-constrained cyclic pentapeptides, either appended to the N-terminus or incorporated within Rev34-50, are efficient helix nucleators in water. They induce up to 90% alpha helicity for isolated Rev peptides in water and confer high RNA-binding affinity.