A cyclic PNA-based compound targeting domain IV of HCV IRES RNA inhibits in vitro IRES-dependent translation

Sergio A Caldarelli; Mohamed Mehiri; Audrey Di Giorgio; Amaury Martin; Olivier Hantz; Fabien Zoulim; Raphael Terreux; Roger Condom; Nadia Patino

doi:10.1016/j.bmc.2005.06.008

A cyclic PNA-based compound targeting domain IV of HCV IRES RNA inhibits in vitro IRES-dependent translation

Bioorg Med Chem. 2005 Oct 15;13(20):5700-9. doi: 10.1016/j.bmc.2005.06.008.

Authors

Sergio A Caldarelli¹, Mohamed Mehiri, Audrey Di Giorgio, Amaury Martin, Olivier Hantz, Fabien Zoulim, Raphael Terreux, Roger Condom, Nadia Patino

Affiliation

¹ Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex, France.

PMID: 16061387
DOI: 10.1016/j.bmc.2005.06.008

Abstract

A cyclic molecule 1 constituted by a hepta-peptide nucleic acid sequence complementary to the apical loop of domain IV of hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA has been prepared via a 'mixed' liquid-phase strategy, which relies on easily available protected PNA and poly(2-aminoethylglycinamide) building blocks. This compound 1 has been elaborated to mimic 'loop-loop' interactions. For comparison, its linear analog has also been investigated. Although preliminary biological assays have revealed the ability of 1 to inhibit in vitro the HCV IRES-dependent translation in a dose-dependent manner, the linear analog has shown a slightly higher activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Hepacivirus / genetics*
In Vitro Techniques
Magnetic Resonance Spectroscopy
Models, Molecular
Peptide Nucleic Acids / chemistry
Peptide Nucleic Acids / drug effects*
Protein Biosynthesis*
RNA, Viral / physiology*
Ribosomes / chemistry*
Spectrometry, Mass, Electrospray Ionization

Substances

Peptide Nucleic Acids
RNA, Viral