Macrophage migration inhibitory factor antagonists and methods of using same
Methods of inhibiting one or more biological activities of Macrophage migration inhibitory factor (MIF) polypeptides are provided using an MIF inhibitory compound. The methods include therapeutic methods for treating cancers and inflammatory diseases.
1. A method of inhibiting a biological activity of a Macrophage migration inhibitory factor (MIF) polypeptide, comprising contacting the MIF polypeptide with a compound having a structure of Formula (I):
wherein:
each R is independently H, halo, OH, alkyl, substituted alkyl, aryl, amino, or carboxyl;
R 1 is iodo;
R 2 is H, halo, OH, alkyl, substituted alkyl, aryl, or amino; and
n is an integer from 0 to 5.
2. The method of claim 1 , wherein the compound forms a stable interaction with at least a methionine at the second N-terminal residue (Met-2) of the MIF polypeptide.
3. The method of claim 2 , wherein the MIF polypeptide comprises a homotrimer of monomers A, B, and C, and monomer A comprises the Met-2(Met-A2).
4. The method of claim 3 , wherein the compound further forms a stable interaction with one or more of Pro-1, Lys-32, Pro-33, Tyr-36, His-62, Ser-63, Ile-64, Lys-66, Tyr-95, Met-101, Val-106, Trp-108 and Phe- 1 13 of the MIF polypeptide.
5. The method of claim 1 , wherein the MIF polypeptide is a mammalian MIF polypeptide.
6. The method of claim 5 , wherein the MIF polypeptide comprises SEQ ID NO:1.
7. A method for inhibiting a biological activity of a Macrophage migration inhibitory factor (MIF) polypeptide, comprising contacting the MIF polypeptide with 4-iodo-6-phenylpyrimidine.