Small-molecule inhibitor: MUGB

Name

History: MUGB was described as a reagent for the spectrofluorimetric titration of some trypsin-like serine peptidases (Jameson et al., 1973).
Peptidases inhibited: Inhibits trypsin, thrombin) and factor Xa (Jameson et al., 1973). Acrosin is also inhibited (Brown et al., 1975). The reaction of MUGB with factor VIIa has been described by Payne et al. (1996).
Mechanism: MUGB is a slowly-hydrolysed substrate of trypsin and many serine peptidases with similar specificity. The rate of acylation of the enzyme is much faster than its deacylation, so that the compound acts as a temporary inhibitor (Jameson et al., 1973). The "burst" of release of 4-methylumbelliferone in the acylation reaction is easily monitored spectrofluorimetrically, and allows determination of the active site molarity of the peptidase (c.f. NPGB: Chase & Shaw, 1969).

Inhibitor class: This compound is of the class of acylating agents of serine peptidases. Such compounds acylate the active site serine to form an acyl enzyme that is much more stable than that formed in normal catalysis, as a result of geometric or electrostatic effects. This class of inhibitors has been reviewed by Powers & Harper (1986) (pp. 108-119) and Powers et al. (2002) (pp. 4695-4728).