Biological and Medicinal Aspects of Peptides and Sugar-Based Boron-Containing Compounds

Boron has proven to be a magic element in synthetic and medicinal chemistry, enabling the development of new chemical reactions and biological activity. The first two boron-containing drugs, bortezomib (BTZ) and ixazomib, are considered dipeptides and have inspired the exploration of other boron-analogs, such as peptide-boron conjugates and novel boron-sugar scaffolds in drug design. Over the years, peptide drugs have enhanced our ability to target enzymes through precise molecular recognition and facilitating protein-drug interactions that are unavailable for small molecules. Sugar-conjugates have added important aspects in drug design by enhancing bioavailability, stability, and targeting tumor cells through sugar receptor interactions. To this end, conjugating boronic acids or esters to therapeutic peptides or sugars can further improve pharmacokinetic and pharmacodynamic properties by initiating reversible covalent binding, improving bioavailability, inducing unique fluorescent properties, and providing alternative uptake mechanisms. Herein, we will discuss the advancements being made in the field of boron medicinal chemistry in terms of boron-containing peptides and sugars, including FDA-approved drugs, chemical biology imaging tools, preclinical compounds, and boron neutron capture therapy (BNCT) delivery agents.