Polyamide Amino Acids trimers as TAR RNA ligands and anti-HIV agents

被引：8

作者：

Bonnard, Vanessa ^{[1
]}

Pascale, Lise ^{[1
]}

Azoulay, Stephane ^{[1
]}

Di Giorgio, Audrey ^{[1
]}

Rogez-Kreuz, Christine ^{[2
]}

Storck, Karine ^{[2
]}

Clayette, Pascal ^{[2
]}

Patino, Nadia ^{[1
]}

机构：

[1] Univ Nice Sophia Antipolis, Inst Chim Nice, UMR CNRS UNSA 6001, Lab Chim Mol Bioact & Aromes, F-06108 Nice, France

[2] CEA, SPI Bio, Neurovirol Dept, F-92265 Fontenay Aux Roses, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 21期

关键词：

Polyamide Amino Acids; TAR RNA ligands; Anti-HIV agents; AFFINITY; TRANSACTIVATION; CONFORMATION; BINDING;

D O I：

10.1016/j.bmc.2010.09.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7432 / 7438

页数：7

共 23 条

[1] Structure of HIV-1 TAB RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge [J].