Synthesis of novel lipophilic nucleotide and CpG dinucleotide conjugates for the stimulation of the immune response system
thesisposted on 01.11.2018 by Maria Goula
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
The research described in this thesis was aimed at synthesizing novel lipophilic nucleotide and CpG dinucleotide conjugates with the purpose of improving their immunostimulatory activity. The first part of the discussion describes the successful synthesis of novel acetal, carbonate, carbamate and ester linkers of tocopherol and cholesterol for attaching lipophilic molecules to the nucleotide constructs. This was done in order to improve transport of the molecules across cell membranes as the lipophilic tail can assist the likelihood of oligonucleotide uptake into the cells by reducing their polarity. Furthermore, a linker was synthesized which was used to link tumour targeting GRE1, GRE4 and G34 rabbit antibodies provided by the labs in Queen's Medical Centre [Nottingham] and Aphton Corporation to different DNA constructs containing antisense insert. The resulting solutions of bound antibodies were purified to give the biologically active antibody constructs. The antibodies retained at the binding sites were eluted and showed biological activity, which unfortunately could not be maintained. [Continues.]