RESUMEN

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.

Asunto(s)

Aminoácidos/química , Fármacos Anti-VIH/química , Duplicado del Terminal Largo de VIH , Nylons/química , ARN Viral/química , Secuencia de Aminoácidos , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/farmacología , Transferencia Resonante de Energía de Fluorescencia , Ligandos , Nylons/síntesis química , Nylons/farmacología , ARN Viral/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/química , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo