Binding of six chimeric analogs of omega-conotoxin MVIIA and MVIIC to N- and P/Q-type calcium channels

Replacement of the N-terminal half of omega-conotoxin MVIIC, a peptide bloc ker of P/Q-type calcium channels, with that of omega-conotoxin MVIIA signif icantly increased the affinity for N-type calcium channels. To identify the residues essential for subtype selectivity, we examined single reverse mut ations from MVIIA-type to MVIIC-type in this chimeric analog A reverse muta tion from Lys(7) to Pro(7) decreased the affinity for both P/Q- and N-type channels, whereas that from Leu(11) to Thr(11) increased the affinity for P /Q-type channels and decreased the affinity for N-type channels. The roles of these two residues were confirmed by synthesizing two MVIIC analogs in w hich Pro(7) and Thr(11) were replaced with Lys(7) and Leu(11), respectively . (C) 2000 Academic Press.