Tripeptides from synthetic amino acids block the Tat-TAR association and slow down HIV spread in cell cultures.
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.
Ludwig
Verena
V
Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
Krebs
Andreas
A
Stoll
Michaela
M
Dietrich
Ursula
U
Ferner
Jan
J
Schwalbe
Harald
H
Scheffer
Ute
U
Dürner
Gerd
G
Göbel
Michael W
MW
D000473:Alkanes / Q000737:chemistry / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D015498:HIV-2 / Q000187:drug effects / Q000254:growth & development; D006367:HeLa Cells; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
D000473:Alkanes; D000596:Amino Acids; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D009842:Oligopeptides; D010446:Peptide Fragments; D011743:Pyrimidines; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; C415751:tat peptide (1-9), Human immunodeficiency virus 1; D001120:Arginine