Our research on Peptide Nucleic Acids (abbreviated as PNAs) focuses on introducing chemical modifications that will make this class of molecules broadly useful to detect sequences of nucleic acids and also to create new type of nano materials for biomedical research. Unique nucleic acid sequences are associated with diseases, pathogens, and many agents associated with bioterrorism. Detection of nucleic acids from these agents can be employed as a method to detect their presence or absence, as well as to monitor progression of a specific disease. Our research involves the synthesis of a class of non-natural molecules (called PNAs) that bind to specific DNA or RNA sequences. We can design our molecules to bind to any sequence of DNA or RNA, and we have found that our molecules are extremely good at selective recognition of HIV RNA. We have continued to refine our assay using our PNA molecules to detect a small amount of HIV in plasma. We also extended a study exploring the potential of sidechain-modified PNAs as basic scaffolds for nanotechnology. Using a system of long DNA sequences, we developed conditions for the self-assembly of specific PNAs onto DNA strands as a way to create nanopatterns of specific biological ligands. We have completed an extensive study using this system to examine the multivalent effects of the dopamine d2 receptor in cellular membranes (which is a G-protein coupled receptor associated with Parkinson's disease).

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12
Fiscal Year
2016
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U.S. National Inst Diabetes/Digst/Kidney
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Tagad, Harichandra D; Debnath, Subrata; Clausse, Victor et al. (2018) Chemical Features Important for Activity in a Class of Inhibitors Targeting the Wip1 Flap Subdomain. ChemMedChem 13:894-901
Debnath, Subrata; Kosek, Dalibor; Tagad, Harichandra D et al. (2018) A trapped human PPM1A-phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity. J Biol Chem 293:7993-8008
Liu, Yanning; Lou, Guohua; Norton, John T et al. (2017) 6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib. FASEB J 31:5453-5465
Gupta, Pankaj; Rastede, Elizabeth E; Appella, Daniel H (2015) Multivalent LK?-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes. Bioorg Med Chem Lett 25:4757-60
Gaynutdinov, Timur I; Englund, Ethan A; Appella, Daniel H et al. (2015) G-quadruplex formation between G-rich PNA and homologous sequences in oligonucleotides and supercoiled plasmid DNA. Nucleic Acid Ther 25:78-84
Dix, Andrew V; Conroy, Jennie L; George Rosenker, Kara M et al. (2015) PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor. ACS Med Chem Lett 6:425-9
Zhao, Chao; Hoppe, Travis; Setty, Mohan Kumar Haleyur Giri et al. (2014) Quantification of plasma HIV RNA using chemically engineered peptide nucleic acids. Nat Commun 5:5079
Englund, Ethan A; Zhang, Ning; Appella, Daniel H (2014) Cyclopentane peptide nucleic acids. Methods Mol Biol 1050:13-8
Englund, Ethan A; Gupta, Pankaj; Micklitsch, Christopher M et al. (2014) PPG peptide nucleic acids that promote DNA guanine quadruplexes. Chembiochem 15:1887-90
Dix, Andrew V; Moss, Steven M; Phan, Khai et al. (2014) Programmable nanoscaffolds that control ligand display to a G-protein-coupled receptor in membranes to allow dissection of multivalent effects. J Am Chem Soc 136:12296-303

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