ISBN 978-3-8439-5283-5

978-3-8439-5283-5, Reihe Organische Chemie

Vasiliki Krupp
Synthese von verzweigten Oligoribonukleotiden für die Bildung neuer Biomaterialien

193 Seiten, Dissertation Universität Stuttgart (2022), Softcover, A5

Zusammenfassung / Abstract

In this thesis the synthesis and application of branched oligonucleotides are reported. Branched oligonucleotides, so-called “DNA hybrids”, consist of an organic core molecule that acts as branching element and is covalently liked to oligonucleotide strands (“DNA hybrid arms”). These molecules have already been successfully synthesized in the Richert Research Group and their potential applications have been investigated. By assembly and subsequent denaturation of a three-dimensional DNA hybrid lattice, the storage and release of active pharmaceutical ingredients and proteins was achieved. One motivation for this work was to synthesize RNA hybrids, which have been poorly studied so far to investigate the ability to form three-dimensional networks. In the first part of the thesis, the adamantane derivative 1,3,5,7-tetrakis (p-hydroxybiphenyl) adamantane (TBA) with CC dinucleotide arms and a propargyl group at the 3'-position of the sugar was synthesized. The introduction of this functional group enabled the simultaneous extension of all four “arms” of the DNA hybrid by one RNA strands, using the copper-catalyzed 1,3-dipolar cycloaddition (CuAAC, CLICK reaction). Two different RNA strands (9mer and 11mer) were synthesized using standard RNA solid-phase synthesis on cpg. The building block 5'-azido-2',5'-deoxythymidine has been synthesized prior to this over three steps and was finally coupled to the immobilized RNA strands. After optimization of this CLICK reaction, two four-fold extended RNA hybrids with 44 and 52 nucleotides were isolated with a yield of 25% and 19% after chromatographic purification, respectively. Two RNA hybrids containing the branching element 1,3,5,7-adamantanetetraol (TOA) were also synthesized for use in the formulation of labile molecules such as mRNA. These RNA hybrids with oligoribonucleotide arms of the sequence 5'-CAUGGU-3' or 5'-UUUUUU-3' were complementary to the rabies virus mRNA sequence.