94 € – 418 €
ω-conotoxin-GVIA (omega conotoxin GVIA) is a conotoxin thath has been isolated from the venom of the cone Conus geographus. ω-conotoxin GVIA acts at presynaptic membranes. It binds and blocks specifically voltage-dependent N-type Ca2+channels Cav2.2 channel with an ED50 of 68pM.
AA sequence: H-Cys1-Lys-Ser-Hyp-Gly-Ser-Ser-Cys8-Ser-Hyp-Thr-Ser-Tyr-Asn-Cys15-Cys16-Arg-Ser-Cys19-Asn-Hyp-Tyr-Thr-Lys-Arg-Cys26-Tyr-NH2
Hyp: hydroxyproline
(Disulfide bonds between Cys1-Cys16, Cys8-Cys19 and Cys15-Cys26)
Length (aa): 27
Formula: C120H182N38O43S6
Molecular Weight: 3036.05 Da
Appearance: White lyophilized solid
Solubility: water and saline buffer
CAS number: [106375-28-4]
Source: Synthetic
Purity rate: > 95 %
The structure-function relationships of the N-type calcium channel blocker, omega-conotoxin GVIA (GVIA), have been elucidated by structural, binding & in vitro & in vivo functional studies of alanine-substituted analogues of the native molecule. Alanine was substituted at all non-bridging positions in the sequence. In most cases the structure of the analogues in aqueous solution was shown to be native-like by 1H NMR spectroscopy. Minor conformational changes observed in some cases were characterized by two-dimensional NMR. Replacement of Lys2 & Tyr13 with Ala caused reductions in potency of more than 2 orders of magnitude in three functional assays (sympathetic nerve stimulation of rat isolated vas deferens, right atrium & mesenteric artery) & a rat brain membrane binding assay. Replacement of several other residues with Ala (particularly Arg17, Tyr22 & Lys24) resulted in significant reductions in potency (<100-fold) in the functional assays, but not the binding assay. The potencies of the analogues were strongly correlated between the different functional assays but not between the functional assays & the binding assay. Thus, the physiologically relevant assays employed in this study have shown that the high affinity of GVIA for the N-type calcium channel is the result of interactions between the channel binding site & the toxin at more sites than the previously identified Lys2 & Tyr13.
