An alpha-helical peptidomimetic inhibitor of the HIV-1 Rev-RRE interaction

Journal of the American Chemical Society
Nicholas L MillsR Kiplin Guy

Abstract

The interaction between the HIV-1 Rev protein and the Rev-Responsive Element (RRE) RNA is an attractive target for anti-viral therapy. We have designed alpha-helical peptidomimetics of Rev-like peptides using side chain-side chain macrolactam formation between positions i and i+4. One peptidomimetic having an appropriate location, orientation, and length of the macrolactam exhibited both significant helical character and specific RRE binding. This molecule displays 2-fold greater RNA specificity than the wild-type Rev peptide and more than 20-fold greater specificity than an uncyclized control peptide. Thus, specific, high affinity recognition of the RRE is feasible utilizing a small, relatively rigid peptidomimetic scaffold.

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Citations

Jul 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Misook OhHyun-Suk Lim
Feb 3, 2016·Frontiers in Bioengineering and Biotechnology·Andrea GroßJutta Eichler
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