A cyclic PNA-based compound targeting domain IV of HCV IRES RNA inhibits in vitro IRES-dependent translation.
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.
Caldarelli
Sergio A
SA
Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex, France.
Mehiri
Mohamed
M
Di Giorgio
Audrey
A
Martin
Amaury
A
Hantz
Olivier
O
Zoulim
Fabien
F
Terreux
Raphael
R
Condom
Roger
R
Patino
Nadia
N
D016174:Hepacivirus / Q000235:genetics*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000187:drug effects*; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000502:physiology*; D012270:Ribosomes / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D020135:Peptide Nucleic Acids; D012367:RNA, Viral