Non-reducible disulfide bond replacement implies that disulfide exchange is not required for hepcidin-ferroportin interaction.

Previous studies have led to opposing hypotheses about the requirement of intermolecular disulfide exchange in the binding of the iron regulatory peptide hepcidin to its receptor ferroportin. To clarify this issue, we used the diaminodiacid approach to replace the disulfide bonds in hepcidin with non-reducible thioether bonds. Our results implied that disulfide exchange is not required for the interaction between hepcidin and ferroportin. This theory is further supported by our development of biologically active minihepcidins that do not show activity dependence on cysteine.