Click chemistry

Click chemistry is a synthesis approach developed for the rapid construction of functional molecules, including new drugs, functional materials and important chemical tools for biology. By their very nature, click reactions are high yielding, wide in scope, create only inoffensive by-products, are specific, simple to perform and can be conducted in easily removable or benign solvents. They enable the unification of discrete units or ‘building blocks’ in a controlled fashion, thereby building-up complexity with exquisite control.

In the Moses group, we focus on the development and application of new functional click chemistry, with particular emphasis on anticancer drug discovery, new antibiotics and chemical biology.

For example, we have employed click chemistry in a number of drug discovery projects, including the development of therapeutic DNA binding ligands that interact with telomeric regions of the genome. This is important because telomere function is involved in cellular maintenance and is particularly relevant for cancer cell survival. We have made a number of telomere binding ligands, which show remarkable selectivity and potency against cancer cells.

In another project, we developed the first fragment based click chemistry approach towards lactate dehydrogenase-5 (LDH5) inhibitors. LDH5 is an important metabolic enzyme, which is believed to be crucial for the survival of tumour cells and particularly those in an oxygen-starved environment. The LDH enzyme has two important regions in it’s active site, and we designed a molecule that can simultaneously bind to both sites and inhibit this key enzyme (see publication Acta Crystallographica Section D, 2014).