Structure-activity relationships of calcicludine and dendrotoxin-I, homologous peptides acting on different targets, calcium and potassium channels

Calcicludine (CaC) and dendrotoxin-I (DTX-I) possess high homology of their primary structures despite their different biological activities acting on calcium and potassium channels, respectively. In order to elucidate the ch annel specificity displayed by these toxins, their three-dimensional struct ures were compared by NMR. These analyses revealed that their overall confo rmations are similar except for the structure at the N-terminus. To demonst rate the significance of this N-terminal, chimeric peptides, CaC(1-30)/DTX- I(31-60) and DTX-I(1-30)/CaC(31-60), were synthesized. The CD spectra and r eceptor-binding measurements of chimeric peptides indicated that the contri bution to the overall conformation and to the affinity of the N-terminal pa rt of molecule seem to be more important than that of the C-terminal one. T hese results suggest that the N-terminal part may participate in distinguis hing between calcium and potassium channels. (C) 1999 Academic Press.