Distinctly different effects of two closely related contryphans have been demonstrated on voltage-activated Ca2+ channels. The peptides Lo959 and Am975 were isolated from Conus loroisii, a vermivorous marine snail and Conus amadis, a molluscivore, respectively. The sequences of Lo959 and Am975 were deduced by mass spectrometric sequencing (MALDI-MS/MS) and confirmed by chemical synthesis. The sequences of Lo959, GCPDWDPWC-NH2 and Am975, GCODWDPWC-NH2 (O: 4-trans-hydroxyproline: Hyp), differ only at residue 3; Pro in Lo959, Hyp in Am975, which is identical to contryphan-P, previously isolated from Conus purpurascens, a piscivore; while Lo959 is a novel peptide. Both Lo959 and Am975 undergo slow conformational interconversion under reverse-phase chromatographic conditions, a characteristic feature of all contryphans reported thus far. Electrophysiological studies performed using dorsal root ganglion neurons reveal that both peptides target high voltage-activated Ca2+ channels. While Lo959 increases the Ca2+ current, Am975 causes inhibition. The results establish that subtle sequence effects, which accompany post-translational modifications in Conus peptides, can have dramatic effects on target ion channels.
V. Sabareesh, K. Gowd, H., Ramasamy, P., Sudarslal, S., Krishnan, K. S., Sikdar, S. K., and Balaram, P., “Characterization of Contryphans from Conus Loroisii and Conus Amadis that Target Calcium Channels”, Peptides, vol. 27, pp. 2647 - 2654, 2006.