Development of New Bioorthogonal Chemistry

The overarching objective of this project is to develop a novel series of molecular tags that can be used to label important biomolecules such as proteins. Proteins are essential chemical signalling molecules whose misfunction is frequently associated with disease. Having the ability to visualise proteins in their natural environment (i.e. inside a cell) is therefore an important emerging technique as identifying their sub-cellular location may offer new insights into disease processes, enabling the development of new medicines for a range of illnesses. Previous results in our laboratory have shown how a small molecule known as a tetrazole, which under normal conditions is chemically inert, can be activated through exposure to ultraviolet light, giving rise to a reactive intermediate which is capable of specifically recognising key features on a protein target. This allows us to chemically modify a protein whilst it is in its natural environment in a cell. Following this encouraging proof of principle, we aim to develop a range of tetrazole systems bearing tags which can be used to visualise a protein in a cell following UV light activation. The tags will be designed to have a range of features that will allow us to study proteins in cells using imaging techniques that are commonly used in other areas of physical science such as infa-red or Raman spectroscopies, as well as fluorescence techniques. Overall, this project will aim to deliver a palette of new molecular tools which can be used in a benign manner to selectively label protein targets of relevance to disease.