Boron containing compounds as protease inhibitors

Reem Smoum*, Abraham Rubinstein, Valery M. Dembitsky, Morris Srebnik

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

332 Scopus citations


The approval of the potent and selective proteasome inhibitor, bortezomib (VELCADE), in 2003, triggered the search for boron compounds with protease inhibition properties that could be used in the clinic. Among those, PT-100 is one that targets dipeptidyl peptidases, such as fibroblast activation protein (FAP). Aryl- and arylalkylboronic acids were the first boronic acids reported to be strong competitive inhibitors of subtilisin and chymotrypsin, and it was likely that these boronic acids act as transition state analogues by forming such tetrahedral enzyme complexes. Peptidyl boronic acids are among the most potent inhibitors of serine proteases known, achieving sub-nanomolar affinity from interaction with the S-subsites alone. Researchers are increasingly looking to boron containing molecules as protease inhibitors. Moreover, there are many interesting applications of some boronic acid compounds which target the HIV proteases. The elucidation of their mechanism of action as anti-HIV agents may lead to more biological targets for boronic acid compounds.

Original languageAmerican English
Pages (from-to)4156-4220
Number of pages65
JournalChemical Reviews
Issue number7
StatePublished - 11 Jul 2012


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