Chemistry Student Seminar: Using boronic-acid based inhibitors as potential cancer therapeutics

Presenter

Dion Turner - Master of Philosophy (Chemistry)

Abstract

Current chemotherapy treatments for multiple myeloma inhibit the β5 subunit of the proteasome to promote apoptosis in cancer cells.

Proteasome inhibitors such as bortezomib (Velcade®) result in severe side effects to a large percentage of patients, such as peripheral neuropathy and low blood cell counts.

Bortezomib also suffers from poor systemic distribution and development of resistance via mutation of the proteasome. As such, there is a considerable need for the development of new proteasome inhibitors.

A belactosin A derivative has shown that the primed site of the β5 subunit of the proteasome is a promising target for interactions to improve specificity. The hydrophilic residues at the end of this site may be able to be reached by designing bortezomib inspired inhibitors with an extended P2 residue.

Further control of the inhibitor’s activity can be achieved with incorporation of an azobenzene photoswitch into the P2 residue. Utilising light to isomerise the inhibitor allows for the inhibitor to be ‘turned on’ in the required areas, reducing off-target effects.