An alpha-helical peptidomimetic inhibitor of the HIV-1 Rev-RRE interaction.
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.
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-2280, USA.
Nicholas L
NL
Mills
Matthew D
MD
Daugherty
Alan D
AD
Frankel
R Kiplin
RK
Guy
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002942:Circular Dichroism; D015694:Gene Products, rev / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015752:Genes, env; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D054321:rev Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015694:Gene Products, rev; D009842:Oligopeptides; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus