Synthesis of peptide nucleic acids for DNA binding studies and bioactive peptides for therapeutic applications in Wilson's Disease and neurodegenerative disorders

Date

2025-3

Author

Kesici, Mehmet Seçkin

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Peptide nucleic acids (PNAs) are synthetic analogs of DNA or RNA in which the ribose-phosphate backbone is changed with a peptide-like backbone structure to increase chemical stability and resistance to enzymatic degradation. This backbone allows PNAs to form highly stable, sequence-specific hybrids with complementary nucleic acids and it makes them powerful tools for genetic diagnostics, antisense therapies, and molecular biology research. In this thesis, there were two unsuccessful attempts followed by successful synthesis of the PNA-2, Ac-TCTCTCTCTC-KKK-NH2 and PNA-3, H-GCTATGTC-NH2, which have been sent to Slovenian NMR Centre for mechanistic studies using dispersive NMR to observe PNA-DNA interactions and interconversions between PNA-DNA complexes. Solid phase peptide synthesis (SPPS) enables the stepwise assembly of amino acid blocks on solid support and increases the efficiency and purity of the peptide and protein synthesis. SPPS is widely used in both research and pharmaceutical industries to produce peptides for diagnostic probes, therapeutic agents and enzyme inhibitors. In this thesis, 30 different peptides were synthesized, purified and vi characterized for the treatment research of various neurodegenerative diseases. In addition, 43 different tripeptides were synthesized and subsequently reduced to their corresponding trientine derivatives (resulting in 47 distinct trientine derivatives) for potential use as treatments for Wilson Disease and other copper-related disorders.

Subject Keywords

PNA, Peptides, SPPS, Trientine

URI

https://hdl.handle.net/11511/114095

Collections

Graduate School of Natural and Applied Sciences, Thesis