Synthesis And Biological Evaluation Of An Iodinated Iberiotoxin Analogue, [Mono-Iodo-Tyr(5), Phe(36)]-Iberiotoxin

The synthesis and iodination of a structural analogue of the specific large-conductance calcium-activated potassium (BK) channel blocker, iberiotoxin (IbTX), a 37-amino acid scorpion neurotoxin, is reported. The synthesis of this analogue, [Tyr(5), Phe(36)]-IbTX, was accomplished using standard solid-phase Fmoc (9-fluorenylmethoxycarbonyl) chemistry protocols. The linear peptide was cyclized via the formation of three intramolecular disulfide bridges and subsequently iodinated at the Tyr(5) position. Upon purification, the iodinated analogue, [mono-iodo-Tyr(5), Phe(36)]-IbTX, exhibited comparable biological activity to native IbTX in blocking BK-mediated currents. These findings suggest the synthesis and use of an I-125 labelled IbTX analogue for BK channel localization in autoradiography experiments. (C) Munksgaard 1996.