1 channel, leaving the peptide setting up in the channel. Although the docking data presented here are preliminary, we could suppose that there are new possibilities for interaction and recognition of K+-channels by scorpion toxins. Considering the low affinity find more of κ-KTxs to Kv1 channels, other molecular targets were

tested in the present work. The synthetic κ-KTx2.5 was not able to affect K+-currents through rKv2.1, rKv3.1, rKv4.2, or rKv4.3 potassium channels, nether to alter the function of Nav1.2, Nav1.3, Nav1.4, Nav1.8, and DmNav1, sodium channels using ion-channels heterologously expressed in Xenopus oocytes. As the toxin did not blocked rKv1.1 and rKv1.4 expressed in Xenopus oocytes even though it blocked human Kv1.1 or Kv1.4 expressed in CHO cells, we suppose the toxin is not a true pore blocker like TTX or several α-KTxs, nor a turret blocker like γ-KTxs, but that it interacts with the phospholipid(s) of the cell membrane surrounding the K+-channel protein. Even in the absence of a clear crystal structure of the toxin bound on the channel, or in the absence of mutagenesis data, it can be speculated that κ-KTx2.5 interacts to the outer region PR-171 solubility dmso of the channel. It can be seen

from the top view in Fig. 7A and the docking, the toxin is not located that far away from the lipid environment. Given the fact that the composition of the cell membrane in oocytes is different, it is possible that oocytes represent not the ideal cell system for proper pharmacology Resminostat of these toxins. In fact, they may be ‘absorbed’ in the vast surface of cell membrane in oocytes, precluding any block as seen in the case of CHO. The κ-KTx folding pattern is unusual in scorpion toxins, but it was described for cytotoxic thionin proteins purified from plants, such as the viscotoxins [25]. For this reason, κ-KTx2.5 was tested against bacterial growth. The κ-KTx2.5 has a net negative charge and pI of 4.92, and although most antimicrobial peptides are usually cationic so that the interaction between the helix and negatively charged membrane of bacteria is facilitated, there are some anionic peptides capable of acting as bactericidal [5] and [33].

We tested the effect of κ-KTx2.5 on E. coli and S. aureus, but up to the concentration of 128 μM, it did not inhibit growth of both types of bacteria. The presence of two prolines in the C-terminus of κ-KTx2.5 is characteristic of bradykinin potentiating peptides, such as those from snakes [8] and [13], and from the scorpion Tityus serrulatus [38]. Despite the presence of proline-proline at the C-terminal, the κ-KTx2.5, in micromolar concentrations, did not show any direct effect in segments of guinea-pig ileum, neither potentiated the bradykinin-stimulated contraction. It is known that bradykynin contracts the ileum by a direct action [4] and part of this effect occurs through production of IP3 [26] which by in turn reduces calcium intracellular levels.