Polyamide amino acids trimers as TAR RNA ligands and anti-HIV agents.
Based on a split-and-mix strategy, a library of trimeric Polyamide Amino Acids (PAA) incorporating four different amino acids (Lys, Ala, Arg, and Phe) has been prepared. Screening of the batches for HIV TAR RNA binding in a fluorescent assay allowed the identification of several components that interact with TAR RNA at a micromolar concentration, with a good TAR versus tRNA specificity. Some of these compounds compete efficiently with the association of TAR and Tat protein. In cell cultures, these compounds display a moderate antiviral activity, associated nevertheless with some toxicity. Overall, these results confirm that this new family can be a basis for the design of novel RNA targeting drugs.
Bonnard
Vanessa
V
Laboratoire de Chimie des Molécules Bioactives et des Arômes, UMR 6001 CNRS UNSA, Institut de Chimie de Nice, Université de Nice Sophia Antipolis, 06108 Nice Cedex, France.
Pascale
Lise
L
Azoulay
Stéphane
S
Di Giorgio
Audrey
A
Rogez-Kreuz
Christine
C
Storck
Karine
K
Clayette
Pascal
P
Patino
Nadia
N
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D016325:HIV Long Terminal Repeat; D008024:Ligands; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D019380:Anti-HIV Agents; D008024:Ligands; D009757:Nylons; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus