A new class of isothiocyanate-based irreversible inhibitors of macrophage migration inhibitory factor.

ABSTRACT: Macrophage migration inhibitory factor (MIF) is a homotrimeric multifunctional proinflammatory cytokine that has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Current therapeutic strategies for targeting MIF focus on developing inhibitors of its tautomerase activity or modulating its biological activities using anti-MIF neutralizing antibodies. Herein we report a new class of isothiocyanate (ITC)-based irreversible inhibitors of MIF. Modification by benzyl isothiocyanate (BITC) and related analogues occurred at the N-terminal catalytic proline residue without any effect on the oligomerization state of MIF. Different alkyl and arylalkyl ITCs modified MIF with nearly the same efficiency as BITC. To elucidate the mechanism of action, we performed detaile

SUBMITTER: Ouertatani-Sakouhi H 

PROVIDER: S-EPMC3607106 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature