Structure and folding of XNA aptamers studied by computational and experimental methods

Aptamers are folded oligonucleotides that bind to a specific target with a high affinity and selectivity. Originally they were composed of natural nucleic acids (RNA or DNA) that are identified in a large library through a process termed Systematic Evolution of Ligands by EXponential enrichment (SELEX). Since natural nucleic acids have short half-life in biological conditions, research shifted to aptamers composed of artificial (xeno) nucleic acids (XNA) with high resistance to chemical en enzymatic degradation. Ignorance on structure and folding of XNA-aptamers currently forms a major roadblock in their way to success. To fill this knowledge gap, computational and experimental methods will be applied in this project to unravel the conformational space that can be occupied by specific XNA species and determine the 2D and 3D structure of selected XNA-aptamers. The project will start to focus on hexitol nucleic acids (HNA) which will be studied in silico using the Assisted Model Building with Energy Refinement (AMBER) package and experimentally through Nuclear Magnetic Resonance (NMR) spectroscopy.