Design of agents interacting with immunoregulating proteins: Potential inhibitors of the phenylpyruvate tautomerase activity catalysed by macrophage migration inhibitory factor (MIF)

The macrophage migration inhibitory factor has been implicated in a number of immune and inflammatory processes. MIF presents particular opportunities for drug design and development with potential therapeutic applications. Drug design strategies taking into consideration of specific stereochemical and tautomeric requirements in the interaction of MIF with substrates and inhibitors allow several novel structures to be de-signed. Our investigations successfully explored the tautomeric and stereochemical aspects of new compounds of the 2-phenylpyruvic acid type, both experimentally, through synthe-sis and structural investigations and computationally, through molecular mechanics and quantum mechanics calculations.