SYNTHESIS AND BIOLOGICAL EVALUATION OF AN IODINATED IBERIOTOXIN ANALOG, [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, ib eriotoxin (IbTX), a 37-amino acid scorpion neurotoxin, is reported. Th e synthesis of this analogue, [Tyr(5), Phe(36)]-IbTX, was accomplished using standard solid-phase Fmoc (9-fluorenylmethoxycarbonyl) chemistr y protocols. The linear peptide was cyclized via the formation of thre e intramolecular disulfide bridges and subsequently iodinated at the T yr(5) position. Upon purification, the iodinated analogue, [mono-iodo- Tyr(5), Phe(36)]-IbTX, exhibited comparable biological activity to nat ive IbTX in blocking BK-mediated currents. These findings suggest the synthesis and use of an I-125 labelled IbTX analogue for BK channel lo calization in autoradiography experiments. (C) Munksgaard 1996.