Small-molecule inhibitor: AEBSF

Name

History: Sulfonyl fluorides were discovered as inhibitors of serine peptidases by Fahrney & Gold (1963).
Peptidases inhibited: AEBSF inhibits many serine peptidase in family S1, especially those with specificity for basic P1 residues. Inhibition has also been reported for dipeptidyl-peptidase IV: Ohkubo et al., 1994), dipeptidyl-peptidase II: Huang et al., 1996) and antibodies with serine-dependent peptidase activity (Odintsova et al., 2005).
Mechanism: Like PMSF, AEBSF reacts with the hydroxyl of the active site serine to form a sulfonyl enzyme that is stable except at high pH.

Inhibitor class: This compound is of the sulfonyl fluoride class. Sulfonyl fluorides were discovered as inhibitors of esterases and serine peptidase inhibitors by Fahrney & Gold (1963). They inhibit serine peptidases such as chymotrypsin (S01.001) by reacting with the hydroxyl of the active site serine residue (sulfonylation) to form a sulfonyl enzyme derivative that is highly stable except at high pH. At high pH a beta-elimination reaction gives rise to the inactive, anhydro derivative of the peptidase (Ako et al., 1972). Sulfonyl fluorides are generally not highly selective. They have been reviewed by Powers et al., 2002, pp. 4735-4736.
Comment: AEBSF is more soluble and more stable than PMSF in aqueous solution.
Reviews: Powers et al. (2002) (pp. 4735-4736) reviews work on peptidase inhibition by AEBSF and many other sulfonyl fluorides.