Stereo-controlled synthesis of artificial genetic systems with modified sugar phosphate backbone

Due to their unique ability to store and transmit genetic information, deoxyribonucleic acids (DNA) and ribonucleic acids (RNA) form the molecular basis of all life. Their genetic code is formed by successive nucleobases, each of which is attached to a sugar. These sugars are linked via phosphodiester bonds. After the discovery of the structure of natural nucleic acids, a large number of modified analogues with altered sugar-phosphate backbones were made with the initial aim of developing nucleic acid-based drugs. However, because natural DNA and RNA degrade very rapidly in the cytoplasm and extracellular environment, they are virtually unusable for medical applications and biological studies. Recently, modified nucleic acids are also being used for various biotechnological applications. To further exploit their potential, user-friendly production methods for these artificial genetic systems are needed. This project aims to achieve this by using a new approach that combines chemical synthesis with enzymatic catalysis for the production of oligonucleotides in which nucleobases are bound to a morpholino ring instead of a sugar. Morpholine rings are linked via a phosphoramidate bond. In the envisaged strategy, first triphosphate analogues of morpholino nucleosides with 4 different nucleobases (adenine, guanine, thymine and cytosine) will be prepared, which will be used as substrate for polymerase-catalysed synthesis of oligonucleotide chains.