Biochemistry of Peptide Nucleic Acids
First reported in 1991, peptide nucleic acids (PNA, for short) are single-stranded molecules designed to recognize nucleic acids in a sequence-selective manner. By design, these synthetic compounds are composed of N-(2-aminoethyl) glycine moiety harboring a nucleobase in such a way that an intact PNA monomer corresponds to an entire nucleoside of natural nucleic acids. these synthetic oligomers presently emerge as an ideal tool to probe natural nucleic acids and thus, they are extensively utilized in biomedical applications including (but not limited to) anti-gene and anti-sense therapies, microarrays, biosensors, and fluorescent in situ hybridization (FISH) assays.
Accordingly, we are interested to investigate the mechanisms of how PNA-DNA adducts are formed through nuclear magnetic resonance studies. We believe that mapping the intermediates throughout these binding events will elucidate the mechanism of how these synthetic peptides recognize natural nucleic acids, as well as to understand why they fail to hybridize with certain sequences of nucleic acids. In collaboration with Assoc. Prof. Dr. Salih Özçubukcu (Chemistry Department, METU) and Slovenian NMR Centre, we have been investigating how PNA oligomers bind and invade natural nucleic acids.
Novel antiviral agents targeting HIV TAT protein
Coined as the main toxin of HIV, TAT protein (trans-activator of transcription) is encoded by the TAT gene in HIV-1. It is a regulatory protein that enhances viral transcription, while simultaneously augmenting the level of transcription of HIV. Upon the initial expression of this protein, some amount of RNA transcripts is produced and this production allows TAT protein to be produced. By binding to cellular factors, and some cellular targets, TAT increases the transcription of the virus by mediating their phosphorylation. As a result of the increased number of Tat protein and HIV gene's transcription, the immunodeficiency of the body diminishes, upon which the body becomes unable to fight back.
In line with its role, targeting TAT protein is of paramount significance to halt HIV infection and to eradicate the virus from the body. In collaboration with Assist. Prof. Dr. Sefer Baday (Istanbul Technical University), we have been working on understanding how TAT protein interacts with cellular proteins. We believe that this research will ultimately lead up to the design of novel antiviral agents targeting HIV TAT protein.