Abstract
Non-natural amino acids with aromatic or heteroaromatic side chains were incorporated into tripeptides of the general structure Arg-X-Arg and tested as ligands of the HIV RNA element TAR. Some of these compounds could compete efficiently with the association of TAR and Tat and downregulated a TAR-controlled reporter gene in HeLa cells. Peptide 7, which contains a 2-pyrimidinyl-alkyl chain, also inhibited the spread of HIV-1 in cell cultures. NMR studies of 7 bound to HIV-2-TAR gave evidence for contacts in the bulge region.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkanes / chemistry
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Alkanes / pharmacology
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Amino Acids / chemistry
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Amino Acids / pharmacology*
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Arginine / analogs & derivatives
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Arginine / pharmacology
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Cells, Cultured
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HIV / drug effects*
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HIV / growth & development
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HIV Long Terminal Repeat / drug effects*
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HIV-1 / drug effects
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HIV-1 / growth & development
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HIV-2 / drug effects
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HIV-2 / growth & development
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HeLa Cells
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Humans
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Hydrocarbons, Aromatic / chemistry
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Hydrocarbons, Aromatic / pharmacology
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Ligands
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Magnetic Resonance Spectroscopy
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Models, Chemical
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Oligopeptides / chemical synthesis
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Oligopeptides / pharmacology*
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Peptide Fragments / antagonists & inhibitors*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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RNA, Viral / chemistry
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RNA, Viral / metabolism
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tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*
Substances
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Alkanes
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Amino Acids
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Hydrocarbons, Aromatic
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Ligands
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Oligopeptides
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Peptide Fragments
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Pyrimidines
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RNA, Viral
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tat Gene Products, Human Immunodeficiency Virus
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tat peptide (1-9), Human immunodeficiency virus 1
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Arginine