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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / metabolism
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Anti-HIV Agents / pharmacology
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Biomimetic Materials / chemistry
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Biomimetic Materials / metabolism
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Biomimetic Materials / pharmacology
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Circular Dichroism
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Gene Products, rev / antagonists & inhibitors*
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Gene Products, rev / genetics
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Gene Products, rev / metabolism
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Genes, env*
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HIV-1 / genetics*
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HIV-1 / metabolism
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Molecular Sequence Data
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Oligopeptides / chemistry*
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Oligopeptides / metabolism
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Oligopeptides / pharmacology*
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Protein Structure, Secondary
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RNA, Viral / genetics
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RNA, Viral / metabolism
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rev Gene Products, Human Immunodeficiency Virus
Substances
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Anti-HIV Agents
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Gene Products, rev
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Oligopeptides
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RNA, Viral
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rev Gene Products, Human Immunodeficiency Virus