BINDING OF THE IMMUNOSUPPRESSANT PEPTIDE CYCLOSPORINE-A TO CALCIUM, ZINC AND COPPER - IS CYCLOSPORINE-A AN IONOPHORE

Cyclosporin A is an immunosuppressant drug that has made organ transpl antation possible during the past decade. This conformationally flexib le peptide, which interferes in an unknown way with calcium-dependent intracellular signalling events, has now been examined in aqueous and acetone solutions containing metal ions. By using electrospray mass sp ectrometry and nuclear magnetic resonance spectroscopy, cyclosporin A was found to bind directly to endogenous metal ions Ca2+, Zn2+ and Cu2 +, With the highest affinity being for Ca2+. These observations raise the possibility that cyclosporins might directly regulate local concen trations of metal ions associated with intracellular signal transducti on. This may be an important clue to the mechanism of immunoregulation by this and structurally related drugs.