IIN Frontiers in Nanotechnology Seminar Series – Daniel Appella
Professor Daniel Appella
National Institutes of Health – NIH
Room- Tech L361
We are developing two classes of chemically-modified peptide nucleic acids and their associated translation to nucleic acid detection and multivalent display platforms. Peptide nucleic acids (PNAs) are synthetic oligomers in which nucleobases are attached to a peptidic backbone consisting of alternating glycine and ethylene diamine units. PNAs bind to complementary nucleic acid sequences following Watson-Crick hydrogen bond pairing rules. We have developed a basic strategy to predictably improve the binding of PNA to complementary nucleic acids by introducing cyclopentane rings into the PNA backbone. This chemical modification routinely increases the thermal stability of PNA binding to nucleic acids by about 5 degrees Celsius per cyclopentane ring. We have used this strategy to develop an effective detection system for nucleic acids associated with HIV. Another PNA modification we have developed is the introduction of a gamma-lysine sidechain into a position of the PNA backbone that will not interfere with DNA binding and which also serves as an attachment point for the multivalent display of ligands. A lysine sidechain is one of the most versatile attachment points for covalent modification in peptides and proteins. By attaching protein binding ligands onto the gamma-lysine sidechains of a PNA, we can use an array of oligonucleotide sequences to probe for multivalent effects in protein receptor binding.