The Hepatitis C virus affects over 200 million people, and inflammatory response can lead to cirrhosis and hepatocellular cancer. A kissing loop tertiary structure exists between two stem loops, 5BSL3.2 in the open reading frame, and SL2 within the 3' X domain of the genome. This kissing loop and a poly-U sequence are essential for replication. Altering the length of or adding cytosine to the poly-U sequence hinders replication. This sequence acts as an unstructured spacer to allow the kissing loop. A modified nucleobase, 2,6-diaminopurine, was studied due to its ability to form three hydrogen bonds to thymine. This nucleobase was bound to various PNA monomers, which were strung together to form oligomers of 4-5 units. These oligomers showed strong binding to the poly-U sequence in vitro. Binding to this poly-U sequence has the potential to alter its conformation and rigidity, disrupt the kissing loop structure, and prevent viral replication.

Targeting the poly-U sequence of the hepatitis c genome with 2,6-diaminopurine PNA oligomers

248th National Meeting (2014)

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