Thesis-2004-Goula.pdf (6.14 MB)
Download fileSynthesis of novel lipophilic nucleotide and CpG dinucleotide conjugates for the stimulation of the immune response system
thesis
posted on 2018-11-01, 15:28 authored by Maria GoulaThe 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.]
Funding
Aphton Corporation.
History
School
- Science
Department
- Chemistry