Among the venomous animals, scorpions [9], [29], [35] and [37] ar

Among the venomous animals, scorpions [9], [29], [35] and [37] are the main source of potassium-channels toxins (KTxs), followed by spiders [7] and [34], Selleckchem PD98059 snakes [12], cone-snail [11] and [36] and sea anemone [1] and [6] peptides. These KTxs show different arrangements of their three-dimensional (3D) structures. The folding types earlier found are: αα, α ββ and βαββ [14], [22] and [23]. Despite the conformation differences, most of these peptides have common residues which promote the binding with the potassium-channel vestibule, such as a lysine residue distant from an aromatic residue for 6.6 ± 1.0 Å [3]. The scorpion KTxs are formed by 20–95 amino acid residues stabilized by two, three or four disulfide

bonds, making this structure relatively stable. The scorpion Z-VAD-FMK mouse KTxs were originally classified into three families named α, β and γ [37], all of them have the highly conserved secondary structural arrangement α/β stabilized by cysteines (CSα/β). More recently, scorpion KTxs presenting a different structural arrangement, with only two α-helices stabilized by two disulfide bonds, CSα/α, were described, and these peptides were named κ-KTxs

[2] and [32]. By possessing the functional dyad for KTxs – the two amino acid residues (Y5 and K19) – their pharmacological targets are thought to be potassium channels. The first κ-KTx described was κ-Hefutoxin1 (systematically named κ-KTx1.1), isolated from the Scorpionidae Heterometrus fulvipes, and that blocks Kv1.2 and Kv1.3 channels at μM concentrations [32]. The κ-KTx1.3, which shows 60% identity with the κ-KTx1.1, was isolated from Heterometrus spinifer, and had blocking activity on Kv1.1, 1.2, and 1.3 channels [24]. The Om-toxins,

isolated from Opisthacanthus P-type ATPase madagascariensis [2], had lower identities (about 20%) with the κ-KTx1.1, 1.2 and 1.3, and have been classified as κ-KTx2.1, 2.2, 2.3 and 2.4. These peptides also have the CSα/α conformation and the presence of the functional dyad – Y5 (or Y4) and K15 residues, but as the κ-KTx1.1 and 1.2, have low affinity to K+-channels. The κ-KTx2.3 caused 70% reduction of K+ currents in Kv1.3 channels, but the effects were obtained at very high concentrations (500 μM) [2]. Using transcriptome approach, we identified in the venom gland of Opisthacanthus cayaporum, two sequences showing high identity to the Omtoxins, OcyC8 and OcyC9 [31]. Here we describe the purification and functional characterization of the mature peptide coded by OcyC8 (GenBank ID: FM998750). This novel κ-KTx is a 28 amino acid long peptide with two disulfide bridges, to which, due to its structural characteristics, it was given the systematic name κ-KTx2.5. As the other κ-KTxs, κ-KTx2.5 was capable of blocking reversibly K+-channels with a Kd at μM concentrations. Due to its low affinity on K+-channels tested, we evaluated the effect of κ-KTx2.

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