AA sequence: TMR-AEEAc-Arg-Ser-Cys3-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys12-Thr-Ala-Phe-Gln-Cys17-Lys-His-Ser-Met-Lys-Tyr-Arg-Leu-Ser-Phe-Cys28-Arg-Lys-Thr-Cys32-Gly-Thr-Cys35-OH
Disulfide bonds: Cys3-Cys35, Cys12-Cys28 and Cys17-Cys32
Length (aa): 35
Formula: C200H310N57O55S7
Molecular Weight: 4611.7 Da
Appearance: red lyophilized solid
Solubility: water or saline buffer
CAS number: NA
Source: Synthetic
Purity rate: > 97%
TMR fluorescent dye (5(6)-TAMRA): λex543nM, λem572nM
TMR-ShK
300 $ – 1. 785 $
Fluorescent (red) Kv1.3 blocker
TMR-ShK peptide toxin is a synthetic derivative of the well-known ShK toxin (Stichodactyla helianthus neurotoxin) isolated from the venom of the Carribean sea anemone Stoichactis helianthus. Wild-type ShK blocks potently Kv1.3 (KCNA3), Kv1.1 (KCNA1), Kv1.4 (KCNA4) and Kv1.6 (KCNA6) with a Kd value of 11 pM, 16 pM, 312 pM and 165 pM, respectively. The fluorescent TMR-labeled ShK blocks Kv1.3 and Kv1.1 with Kd values of 52 pM and 397 pM, respectively. TMR-ShK can be used to identify lymphocytes expressing Kv1.3 channels such as effective memory T cells (TEM) in the case of autoimmune diseases (type 1 diabetes, mellitus or rheumatoid arthritis) which overexpress Kv1.3 channels.
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A Novel Fluorescent Toxin to Detect and Investigate Kv1.3 Channel Up-regulation in Chronically Activated T Lymphocytes
T lymphocytes with unusually high expression of the voltage-gated Kv1.3 channel (Kv1.3(high) cells) have been implicated in the pathogenesis of experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We have developed a fluoresceinated analog of ShK (ShK-F6CA), the most potent known inhibitor of Kv1.3, for detection of Kv1.3(high) cells by flow cytometry. ShK-F6CA blocked Kv1.3 at picomolar concentrations with a Hill coefficient of 1 and exhibited >80-fold specificity for Kv1.3 over Kv1.1 and other K(V) channels. In flow cytometry experiments, ShK-F6CA specifically stained Kv1.3-expressing cells with a detection limit of approximately 600 channels per cell. Rat and human T cells that had been repeatedly stimulated 7-10 times with antigen were readily distinguished on the basis of their high levels of Kv1.3 channels (>600 channels/cell) and ShK-F6CA staining from resting T cells or cells that had undergone 1-3 rounds of activation. Functional Kv1.3 expression levels increased substantially in a myelin-specific rat T cell line following myelin antigen stimulation, peaking at 15-20 h and then declining to baseline over the next 7 days, in parallel with the acquisition and loss of encephalitogenicity. Both calcium- and protein kinase C-dependent pathways were required for the antigen-induced Kv1.3 up-regulation. ShK-F6CA might be useful for rapid and quantitative detection of Kv1.3(high) expressing cells in normal and diseased tissues, and to visualize the distribution of functional channels in intact cells.Beeton C., et al. (2003) A Novel Fluorescent Toxin to Detect and Investigate Kv1.3 Channel Up-regulation in Chronically Activated T Lymphocytes. JBC. PMID: 12511563