Acetyl-[Asn30,Tyr32]-calcitonin fragment 8-32 forms channels in phospholipid planar lipid membranes.

The N-terminally truncated derivative of salmon calcitonin (sCt) (acetyl-[Asn(30),Tyr(32)]-calcitonin fragment 8-32) (AC 187) lacks hormonal activity and is a potent and selective antagonist of the hormone and amylin receptor. It was investigated for its capability to interact and form channels in palmitoleoylphosphatidylcholine:dioleoylphosphatidylglycerol planar lipid membranes. Interestingly, AC 187 exhibits channel activity, whose parameters, i.e., central conductance (Lambda (c)), occurrence (number of channels/min), voltage-dependence and lifetime, are similar to those found for sCt although, in the same experimental conditions, it takes longer to incorporate into the membrane than sCt. This channel activity can be modulated by changing either the holding potential or the pH of the medium, or by adding picomolar concentrations of SDS. One evident difference between the two peptides is that sCt is unselective (1.03) while AC 187 displays a cationic selectivity (P (K) (+)/P (Cl) (-) = 2.7) at pH 7, increasing to 3.87 when the pH drops to 3.8. The present findings indicate that the 1-7 disulfide bridge is sufficient but not necessary for membrane interaction, in accordance with the observation reported on the interaction with membrane receptors. Furthermore, the remarkable pH dependence of the cationic channel could be taken into consideration for full biotechnological study.