The design and synthesis of new anticancer agents targeting DNA (SEARCEYM_U21SCIPVC)

Double stranded DNA is the classical structure that is well known and is the target for many antitumour agents that are currently used in the clinic. Over the last 20 years, higher order DNA has come to the fore as a potential target for the design of new, more selective anticancer agents and a plethora of molecules have been shown to bind to G-quadruplex and i-motif structures. A less well studied but simpler motif is that of the four-way junction, in which, for example, loops in the duplex structure form opposite one another. Several years ago, we showed that ligands could bind to four way junctions (1) and that it was possible to identify molecules that could promote the formation of such structures (2). Work by Segall and coworkers has shown that peptides can also bind to four way junctions and have both antibacterial and antitumour activity (3). We have also recently shown that it is possible to move from peptide structures to more drug like small molecules (4). In this project, we will investigate and design small molecules to target four way junction structures that are more drug like that our previous compounds. We will then test those compounds for antitumour and antibacterial activity. Ultimately our aim is to develop new molecules for a new target that will have potential as therapeutic agents.  

For more information on the supervisor for this project, please go here.

This is a PhD programme. The start date is 1st October 2021. The mode of study is full time. The studentship length is 3 years.

Entry requirements: 2:1 in Chemistry, pharmacology and drug discovery, pharmacy or related.