Boron is an abundant element on earth yet, despite its availability, C-B bonds are not present in the structures of natural products. This, however, does not mean that boron has no utility in chemical biology and drug discovery. On the contrary, there are numerous examples of bioactive molecules that bear C-B bonds. Similar to the synthetic utility of organoboron compounds, the biological activity of boron-containing molecules is based on reversible covalent interactions with nucleophiles. Based on boron’s capacity to covalently bind to biological targets, it is tempting to assume that an organoboron compound is just another electrophile, similar to the “usual suspects” of chemical biology, namely acrylates, epoxides, and aldehydes. However, our analysis of well-known covalent inhibitors suggests that boron is unique in its chameleonic ability to display a range of coordination modes upon interaction with protein targets. This lecture will present the foundational principles of Boroscan – an enabling technology to construct boron-containing bioactive molecules. This toolkit owes its effectiveness to amphoteric boron-containing molecules that serve as key structural units.

Boroscan: An enabling technology for the discovery of bioactive molecules containing boron

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.