A short PNA targeting coxsackievirus B3 5'-nontranslated region prevents virus-induced cytolysis.
Targeting regulatory RNA regions to interfere with the biosynthesis of a protein is an intriguing alternative to targeting a protein itself. Regulatory regions are often unique in sequence and/or structure and, thus, ideally suited for specific recognition with a low risk of undesired side effects. Targeting regulatory RNA elements, however, is complicated by their complex three-dimensional structure, which poses kinetic and thermodynamic constraints to the recognition by a complementary oligonucleotide. Oligonucleotide mimics, which shift the thermodynamic equilibrium towards complex formation and yield stable complexes with a target RNA, can overcome this problem. Peptide nucleic acids (PNA) represent such a promising class of molecules. PNA are very stable, non-ionic compounds and they are not sensitive to enzymatic degradation. Yet, PNA form specific base pairs with a target sequence. We have designed, synthesised and characterised PNA able to enter infected cells and to bind specifically to a control region of the genomic RNA of coxsackievirus B3 (CVB3), which is an important human pathogen. The results obtained by studying the interaction of such PNA with their RNA target, the entrance into the cell and the viral inhibition are herein presented.
Musumeci
Domenica
D
Istituto di Biostrutture e Bioimmagini, CNR, I-80134 Naples, Italy.
Valente
Margherita
M
Capasso
Domenica
D
Palumbo
Rosanna
R
Görlach
Matthias
M
Schmidtke
Michaela
M
Zell
Roland
R
Roviello
Giovanni N
GN
Sapio
Roberto
R
Pedone
Carlo
C
Bucci
Enrico M
EM
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000821:virology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D029822:Enterovirus B, Human / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D020135:Peptide Nucleic Acids; D012367:RNA, Viral