231 € – 1210 €
GrTx1 toxin is a peptide originally isolated from the venom of the spider Grammostola rosea. GrTx1 preferentially blocks voltage-gated sodium channels.
GrTx1 toxin is in the same cluster than other famous sodium channel blockers such as ProTx-II, GsAF-1 and GsAF-2. GrTx1 potently and selectively blocks tetrodotoxin-sensivite channels. IC50 values for Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6 and Nav1.7 have respectively been described to be of 0.63 µM, 0.23 µM, 0.77 µM, 1.29 µM, 0.63 µM and 0.37 µM.
AA sequence: YCQKWMWTCDSKRKCCEDMVCQLWCKKRL-OH
Disulfide bonds: Cys6-Cys16, Cys9-Cys21 and Cys15-Cys25
Length (AA): 29
Formula: C159H243N45O41S8
Molecular Weight: 3697,49 Da
Appearance: White lyophilized solid
Solubility: water
CAS number:
Source: Synthetic
Purity rate: > 95 %
Venom-derived peptide modulators of ion channel gating are regarded as essential tools for understanding the molecular motions that occur during the opening and closing of ion channels. In this study, we present the characterization of five spider toxins on 12 human voltage-gated ion channels, following observations about the target promiscuity of some spider toxins and the ongoing revision of their “canonical” gating-modifying mode of action. The peptides were purified de novo from the venom of Grammostola rosea tarantulas, and their sequences were confirmed by Edman degradation and mass spectrometry analysis. Their effects on seven tetrodotoxin-sensitive Na(+) channels, the three human ether-à-go-go (hERG)-related K(+) channels, and two human Shaker-related K(+) channels were extensively characterized by electrophysiological techniques. All the peptides inhibited ion conduction through all the Na(+) channels tested, although with distinctive patterns. The peptides also affected the three pharmaceutically relevant hERG isoforms differently. At higher concentrations, all peptides also modified the gating of the Na(+) channels by shifting the activation to more positive potentials, whereas more complex effects were recorded on hERG channels. No effects were evident on the two Shaker-related K(+) channels at concentrations well above the IC(50) value for the affected channels. Given the sequence diversity of the tested peptides, we propose that tarantula toxins should be considered both as multimode and target-promiscuous ion channel modulators; both features should not be ignored when extracting mechanistic interpretations about ion channel gating. Our observations could also aid in future structure-function studies and might help the development of novel ion channel-specific drugs.
This communication reports the chemical and physiological characterization of a novel peptide (GrTx1) isolated from the venom of the “rosean-tarantula”Grammostola rosea. This component was one among more than 15 distinct components separated from the soluble venom by high-performance liquid chromatography (HPLC). GrTx1 has 29 amino-acid residues, compactly folded by three disulfide bridges with a molecular weight of 3697 Da. Here we show that this peptide blocks Na(+) currents of neuroblastoma F-11 cells with an IC(50) of 2.8+/-0.1 microM, up to a maximum of about 85% at 10 microM. Moreover, the right-shift (+20.1+/-0.4 mV) of the fractional voltage-dependent conductance could be also compatible with a putative “gating-modifier” mechanism. No effects were seen on common K(+) channels, such as K(v)1.1 and 1.4, using concentrations of toxin up to 10 microM. Sequence analysis reveals that GrTx1 is closely related to other spider toxins reported to affect various distinct ion channel functions. A critical analysis of this study suggests the necessity to search for other potential receptor sites in order to establish the preferred specificity of these kind of peptides.
