SYNTHESIS OF A PHOTOAFFINITY-LABELING ANALOG OF THE INACTIVATING PEPTIDE OF THE SHAKER-B POTASSIUM CHANNEL

A photoactivatable derivative of the inactivating peptide of the Shake r B potassium channel (ShB peptide) has been synthesized from ShB pept ide containing an added cysteine residue at the peptide carboxy-termin us and 1-(p-azidosalicylamido)-4-(iodoacetamido)butane. The peptide de rivative restores rapid inactivation in the deletion mutant Shaker B D elta 6-46 potassium channel in a manner indistinguishable from that of the wild-type ShB peptide, Also, both peptides display similar confor mational behavior when challenged in vitro by an artificial model targ et that partly imitates the properties of the putative receptor site f or the inactivating peptide in the Shaker B potassium channel, Therefo re, we conclude that both functionally and conformationally the photor eactive peptide derivative is an adequate analogue of the wild-type Sh B peptide, suitable for photoaffinity labeling of its binding site in the Shaker B potassium channel, Moreover, because the ShB peptide also serves as an efficient inactivating peptide for a large variety of ot her potassium channels, it appears that the photoreactive analogue may be useful to explore homologous sites in many different channel prote ins.