Helix-stabilizing effects of the pentapeptide KIFMK and its related peptides on the sodium channel inactivation gate peptides

We have previously found by NMR and CD spectroscopic studies that the helic al content of the sodium channel inactivation gate-related peptide (Ac-GGQD IFMTEEQK-NH2; MP-1A) in 80% trifluoroethanol solutions was increased by add ing a pentapeptide, KIFMK. In order to study in further detail whether the presence of the IFM motif and the two lysine residues is a prerequisite for stabilizing the helical conformation, we examined interactions between var ious oligopeptides (RIFMR, KIFMTK, KIQMK, KAFAK, KIIIK) and MP-1A and its r elated peptides; that is, MP-2A in which Phe was replaced by Gln, MP-1MMA i n which Thr was replaced by Met, MP-1TA in which Thr was removed from MP-1A , and MP-1A in which L-Phe was replaced by D-Phe. It was found that the IFM motif was absolutely necessary in both the oligopeptide and the inactivati on gate peptide. This finding means that hydrophobic interactions are opera tive between KIFMK and MP-1A. In contrast, KIFMK destabilized the helical s tructure of MP1-1MMA, MP-1TA, and MP-1A', showing that the conformation aro und the IFM motif in the inactivation gate peptides is an important factor. It was concluded that the IFM motif and the two Lys residues are a prerequ isite for effectively stabilizing the alpha -helix of MP-1A.