The synthesis of novel G-quadruplex ligands and Host-Guest binding evaluation using DOSY NMR


Session type:

Adam Le Gresley

Kingston University, Kingston-Upon-Thames, UK



The ends of chromosomes within animal and human cells possess a guanine rich overhang (telomere). During cell division a number of these guanine groups are lost. Eventually the number of Guanine groups is reduced to the point that cell defence mechanisms destroy the cell.1,2

Within cancer cells an enzyme called telomerase adds additional guanine bases on the ends of the chromosomes making them theoretically immortal. As telomerase is expressed in over 80% of all tumour cells it has become an increasingly important target in the search for better anti-cancer drugs.3,4,5

Method and Results

We report the optimisation of a High-throughput 1H Diffusion Ordered Spectroscopy (DOSY) technique to evaluate the G-quadruplex binding efficacy of small molecules and the synthesis of a series of novel anthracene-based G-quadruplex ligands.

Using in vitro preparations of a G-quadruplex forming oligonucleotide, we are able to observe the interaction of planar small molecules within the stacked G-tetrad structure of the quadruplex. Based on the structure of known, effective G-quadruplex ligands a number of diacrylamido anthracene derivatives have been synthesised via a modified Heck Reaction, which according to the 1H DOSY NMR show good binding to the in vitro G-quadruplex formed and potential as a new class of ligand with anti-cancer properties.


[1] McClintock, B.; Genetics, 1941, 26, 234-282.

[2] Zhu, J.; Wang. H.; Bishop, J.; Blackburn, E. H.; Proc Nat. Acad. Sci. USA.