3,4-Dichloroisocoumarin, a serine protease inhibitor, inactivates glycogen phosphorylase b.

3,4-Dichloroisocoumarin (3,4-DCI) is a highly reactive, mechanism-based inhibitor of serine proteases. We show here that glycogen phosphorylase b is also inactivated by this inhibitor, in a mechanism that parallels the inactivation of serine proteases, but involving multiple sites of covalent modification. Such a process may compromise studies in which 3,4-DCI is used to arrest proteolysis of a second native protein which may itself be modified.