Helical cyclic pentapeptides constrain HIV-1 Rev peptide for enhanced RNA binding

Authors

Rosemary S. Harrison, University of Queensland
Nicholas E. Shepherd, University of Queensland
Huy N. Hoang, University of Queensland
Renee L. Beyer, University of Queensland
Gloria Ruiz-Gomez, University of Queensland
Michael J. Kelso, University of QueenslandFollow
W Mei Kok, University of Queensland
Timothy A. Hill, University of Queensland
Giovanni Abbenante, University of Queensland
David P. Fairlie, University of Queensland

RIS ID

99359

Publication Details

Harrison, R. S., Shepherd, N. E., Hoang, H. N., Beyer, R. L., Ruiz-Gomez, G., Kelso, M. J., Mei Kok, W., Hill, T. A., Abbenante, G. & Fairlie, D. P. (2014). Helical cyclic pentapeptides constrain HIV-1 Rev peptide for enhanced RNA binding. Tetrahedron: the international journal for the rapid publication of full original research papers and critical reviews in organic chemistry, 70 (42), 7645-7650.

Abstract

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.