Cys25 – C-terminal amidation
- Chen, J. et al. (2021) Acta Pharm. Sin. B., 11, 2685.
- Alomone Labs ω-conotoxin Bu8 inhibits CaV2.2 channel currents heterologously expressed in Xenopus oocytes.A. Representative time course of ω-conotoxin Bu8 (#STC-180) inhibition of CaV2.2 (α1B + α2δ1 + β1) channels current. Membrane potential was held at -100 mV, current was elicited by a 100 ms voltage ramp to +60 mV every 10 sec, and inhibited by 10 nM ω-conotoxin Bu8 (green).
B. Superimposed traces of CaV2.2 currents after application of control (black) and of 10 nM ω-conotoxin Bu8 (green), taken from the recording in A.
ω-conotoxin Bu8 (Bu8) is a 25 amino acid peptidyl toxin that was synthesized from the venom of the cone snail, Conus bullatus1. This toxin potently and selectively blocks N-type voltage-gated calcium (Cav2.2) channels. Bu8 displays higher or similar analgesic activity in the pain models compared to MVIIA but has less adverse effects1.
Bu8 adopts a canonical globular scaffold, demonstrated as an inhibitory cysteine knot motif, marked by 3 disulfide bonds that is consistent for all ω-conotoxins in the all-crossing pattern of 1-4, 2-5, and 3-61.
Cav2.2 are predominantly expressed in nerve terminals and are involved in the regulation of neuronal excitability and nociceptive signaling. These channels are multifunctional and play important roles in the transduction of acute and chronic pain perception. They are able to transduce electrical activity into other cellular functions, regulate calcium homeostasis, and process pain information. Since ω-conotoxins selectively inhibit Cav2.2 in nociceptors, they are considered attractive molecules for drug design2.
ω-Conotoxin Bu8 (#STC-180) is a highly pure, synthetic, and biologically active peptide toxin.