This thesis reports on the synthesis and application of branched oligonucleotides, known as “DNA hybrids,” which feature an organic core molecule as a branching element covalently linked to oligonucleotide strands. These hybrids have been successfully synthesized in the Richert Research Group, with investigations into their potential applications. Notably, a three-dimensional DNA hybrid lattice was assembled and denatured, enabling the storage and release of active pharmaceutical ingredients and proteins. A key motivation was to synthesize RNA hybrids, which have been less explored, to study their capacity for forming three-dimensional networks. The thesis first describes the synthesis of the adamantane derivative 1,3,5,7-tetrakis (p-hydroxybiphenyl) adamantane (TBA) with CC dinucleotide arms and a propargyl group at the 3'-position. This functional group facilitated the extension of all four DNA hybrid arms by RNA strands through the copper-catalyzed 1,3-dipolar cycloaddition (CuAAC, CLICK reaction). Two RNA strands (9mer and 11mer) were synthesized via standard RNA solid-phase synthesis. Following optimization, two RNA hybrids with 44 and 52 nucleotides were isolated with yields of 25% and 19%. Additionally, RNA hybrids containing the branching element 1,3,5,7-adamantanetetraol (TOA) were synthesized for formulating labile molecules like mRNA, with sequences complementary to the rabies virus mRNA.
