Abstract
The turripeptide ubi3a was isolated from the venom of the marine gastropod Unedogemmula bisaya, family Turridae, by bioassay-guided purification; both native and synthetic ubi3a elicited prolonged tremors when injected intracranially into mice. The sequence of the peptide, DCCOCOAGAVRCRFACC-NH 2 (O = 4-hydroxyproline) follows the framework III pattern for cysteines (CC–C–C–CC) in the M-superfamily of conopeptides. The three-dimensional structure determined by NMR spectroscopy indicated a disulfide connectivity that is not found in conopeptides with the cysteine framework III: C 1 –C 4, C 2 –C 6, C 3 –C 5 . The peptide inhibited the activity of the α9α10 nicotinic acetylcholine receptor with relatively low affinity (IC 50, 10.2 μM). Initial Constellation Pharmacology data revealed an excitatory activity of ubi3a on a specific subset of mouse dorsal root ganglion neurons.