Smartox Biotechnology
 
작성일 : 14-03-15
[Smartox Biotechnology] New peptide toxins from Smartox Biotechnology
Hainatoxin III / α-conotoxin PeIA / TMR-ShK / μ-conotoxin GIIIB / α-conotoxin GID

New peptide toxins from Smartox Biotechnology
 
Hainantoxin-III
Selective blocker of TTX-S VGSC
 
Hainantoxin-III (HNTX-III) is a peptide that has been isolated from the venom of the Chinese bird spider Seleconosmia
hainana. Hainantoxin-III specifically blocks mammalian neuronal tetrodotoxin-sensitive voltage-gated sodium channels
(VGSCs). Hainantoxin III was found inactive on tetrodotoxin-resistant VGSCs and voltage-gated Ca2+ channels (both high
and low voltage-activated).
Hainantoxin-III strongly depressed the amplitude of rat DRG tetrodotoxin-sensitive Na+ currents with an IC50 value of
1.1 nM. Like Hainantoxin-IV, Hainantoxin-III causes a hyperpolarizing shift of about 10 mV in the voltage midpoint of
 
steady-state Na+ channel inactivation. Similar to Huwentoxin-IV, Hainantoxin-III and Hainantoxin-IV do not affect the
activation and inactivation kinetics of Na+ currents.
Hainantoxin-III inhibits Nav1.7 current amplitude without significantly altering the activation and inactivation kinetics.
Hainantoxin-III increases the deactivation of the Nav1.7 current after extreme depolarizations. Hainantoxin-III seems to
interact with site 4 and to trap the domain II voltage sensor in the closed state. The inhibition of Nav1.7 by hainantoxin-
III is reversible upon washing, but no reversibility was observed for Hainantoxin-IV and Huwentoxin-IV. Hainantoxin-III
was shown to block Nav1.1, Nav1.2, Nav1.3 and Nav1.7 expressed in HEK293 cells with IC50 values of 1.27 µM, 275 nM,
491 nM and 232 nM, respectively.
 
Details
AA sequence:
 
Gly-Cys2-Lys-Gly-Phe-Gly-Asp-Ser-Cys9-Thr-Pro-Gly-Lys-Asn-Glu-Cys16-Cys17-Pro-Asn-Tyr-Ala-Cys22-Ser-Ser-Lys-His-Lys-Trp-Cys29-Lys-Val-Tyr-Leu-NH2
 
(Disulfide bonds between Cys2-Cys17, Cys9-Cys22, Cys16-Cys29)
Length (aa):
 
33
Formula:
C154H228N44O4S6
Molecular Weight:
 
3608.20 Da
Appearance:
 
White lyophilized solid
Solubility:
 
Water and saline buffer
CAS number:
Not available
Source:
 
Synthetic
Purity rate:
 
> 97 %
 
References
1. Wang W., et al. (2003) Determination of disulfide bridges of two spider toxins: Hainantoxin-III and Hainantoxin-IV.
   J Venom Anim Toxins incl Trop Dis. PubMed link
2. Liu Z., et al. (2013) Structure and Function of Hainantoxin-III, a Selective Antagonist of Neuronal Tetrodotoxin-sensitive
   Voltage-gated Sodium Channels Isolated from the Chinese Bird Spider Ornithoctonus hainana. JBC. PubMed link
 
 
α-conotoxin PeIA
Discriminates between α9α10 and α7 nAChRs
 
α-conotoxin PeIA has been isolated from the venom of Conus pergrandis. α-conotoxin PeIA discriminates between α9α10
and α7 nicotinic acetylcholine receptors (AChRs) with IC50 values of 7-50 nM (depending of the authors) and 1.8 µM,
respectively.
The toxin is also known to block α3β2 nicotinic AChRs (with an IC50 of 97 nM) and block voltage-gated N-type Ca2+
channels in rat DRG neurons with an IC50 of 1.1 nM. No significant inhibition of ACh-evoked currents for nicotinic α4β2
and muscle αβγδ AChRs by 1 µM α-conotoxin PeIA was observed. The action of α-conotoxin PeIA is fully reversible
after washout of the peptide in the extracellular medium.
 
Details
AA sequence:
 
Gly-Cys2-Cys3-Ser-His-Pro-Ala-Cys8-Ser-Val-Asn-His-Pro-Glu-Leu-Cys16-NH2
 
(Disulfide bonds between Cys2-Cys8, Cys3-Cys16 )
Length (aa):
 
16
Formula:
C65H98N22O21S4
Molecular Weight:
 
1651.9 Da
Appearance:
 
White lyophilized solid
Solubility:
 
Water or saline buffer
CAS number:
Not available
Source:
 
Synthetic
Purity rate:
 
> 99 %
 
References
1. Day N., et al. (2011) Structure and Activity of α-Conotoxin PeIA at Nicotinic Acetylcholine Receptor Subtypes and
   GABAB Receptor-coupled N-type Calcium Channels. JBC. PubMed link
2. McIntosh M., et al. (2005) A novel α-conotoxin, PeIA, cloned from Conus Pergrandis, discriminates between rat
   α9 α10 and α7 nicotinic cholinergic receptor. JBC. PubMed link
 
 
TMR-ShK - Stichodactyla toxin
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.
 
Details
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 between 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:
Not available
Source:
 
Synthetic
Purity rate:
 
> 97 %
TMR fluorescent dye
 
(5(6)-TAMRA): λex543nM,  λem572nM
 
References
1. Beeton C., et al. (2003) A Novel Fluorescent Toxin to Detect and Investigate Kv1.3 Channel Up-regulation in Chronically
    Activated T Lymphocytes. JBC. PubMed link
2. Tarcha EJ., et al. (2012) Durable pharmacological responses from the peptide ShK-186, a specific Kv1.3 channel
    inhibitor that suppresses T cell mediators of autoimmune disease. J Pharmacol Exp Ther. PubMed link
3. Gilhar A., et al. (2011) The beneficial effect of blocking Kv1.3 in the psoriasiform SCID mouse model.
    J Invest Dermatol. PubMed link
4. Chen R., et al. (2011) Modeling the binding of three toxins to the voltage-gated potassium channel (Kv1.3).
    Biophys J. PubMed link
5. Grgic I., et al. (2009) Blockade of T-lymphocyte KCa3.1 and Kv1.3 channels as novel immunosuppression strategy to
    prevent kidney allograft rejection. Transplant Proc. PubMed link
6. Jin L, Wu Y. (2007) Molecular mechanism of the sea anemone toxin ShK recognizing the Kv1.3 channel explored by
    docking and molecular dynamic simulations. J Chem Inf Model. PubMed link
7. Panyi G, et al. (2006) K+ channel blockers: novel tools to inhibit T cell activation leading to specific 
    innunosuppression.
   Curr Pharm Des. PubMed link
8. Yan L., et al. (2005) Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels.
    Mol Pharmacol. PubMed link
9. Beeton C., et al. (2005) Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy
     of autoimmune diseases. Mol Pharmacol. PubMed link
10.Norton RS., et al. (2004) Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple
     sclerosis and other autoimmune diseases. Curr Med Chem. PubMed link
11.Tudor, J. E., et al. (1996) Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone,
     Nat Struct Biol. PubMed link
12.Pennington MW., et al. (1996) An essential binding surface for ShK toxin interaction with rat brain potassium channels.
     Biochemistry. PubMed link
13.Castaneda, O., et al. (1995) Characterization of a potassium channel toxin from the Caribbean Sea anemone
     Stichodactyla helianthus, Toxicon. PubMed link
 
 
µ-conotoxin GIIIB
Selective blocker of Nav1.4 channels
 
µ-conotoxin GIIIB is a 22-mer peptide originally isolated from the venom of the piscivorous marine snail Conus
geographus.
µ-conotoxin GIIIB adopts a compact structure consisting of a distorted 310-helix and a small ß-hairpin. µ-conotoxin GIIIB is
stabilized by three disulphide bridges and is highly enriched in lysine and arginine residues, forming potential sites of
interaction with Na channels. An unusual feature is the presence of three hydroxyproline residues. µ-conotoxin GIIIB is a
useful probe to discriminate between neuronal and muscle sodium channels as it exhibits at least a 1000-fold specificity for
muscle versus nerve sodium channels. µ-Conotoxin GIIIB selectively blocks Nav1.4 (µ1) voltage-dependent sodium
channels, which are predominantly expressed in muscle, with an affinity close to 20 nM. µ-Conotoxin GIIIB appears to
physically occlude the channel pore by binding on site I of the Na+ channel.
 
Details
AA sequence:
 
Arg-Asp-Cys3-Cys4-Thr-Hyp-Hyp-Arg-Lys-Cys10-Lys-Asp-Arg-Arg-Cys15-Lys-Hyp-Met-Lys-Cys20-Cys21-Ala-NH2
 
(Disulfide bonds between Cys3-Cys15, Cys4-Cys20 and Cys10-Cys21)
Length (aa):
 
22
Formula:
C101H175N39O30S7
Molecular Weight:
 
2640.26 Da
Appearance:
 
White lyophilized solid
Solubility:
 
Water adn saline buffer
CAS number:
Not available
Source:
 
Synthetic
Purity rate:
 
> 97 %
 
References
1. Gregory N. Filatov and Mark M. Rich (2004) Hyperpolarized shifts in the voltage dependence of fast inactivation of
   Nav1.4 and Nav1.5 in a rat model of critical illness myopathy. J. Physiol. PubMed link
2. Cruz LJ, et al. (1985) Conus geographus toxins that discriminate between neuronal and muscle sodium channels.
   JBC. PubMed link
3. Ronald A. Li, et al. (2000) Novel Structural Determinants of m-Conotoxin (GIIIB) Block in Rat Skeletal Muscle (m1)
   Na+ Channels. JBC. PubMed link
4. Ronald A. Li, et al. (2003) Molecular Basis of Isoform-specific μ-Conotoxin Block of Cardiac, Skeletal Muscle, and Brain
   Na+ Channels. JBC. PubMed link
 
 
α-conotoxin GID
Blocker of α3β2, α7 and α4β2 nAChRs
 
α-conotoxin GID is a peptide originally isolated from the venom of the Conus geographus. It is composed of 19 amino
acids and is folded by two disulphide bonds connecting Cys1-Cys3 and Cys2-Cys4. Based on the number of amino acids
between the second and the third cysteine residues (loop I) and the third and fourth cysteine residues (loop II),
 
α-conotoxin GID belongs to the α4/7-conotoxin family. α-conotoxin GID blocks selectively  neuronal nicotinic acetylcholine
receptors with IC50 values of 3 nM (α3β2 nicotinic receptors), 5 nM (α7) and 150 nM (α4β2). α-conotoxin GID is at least 1000-fold less potent onto the α1β1γδ, α3β4, and α4β4 nicotinic receptors. α-conotoxin GID is a unique α4/7-conotoxin because
of its ability to block both α7 and α3β2 isoforms, contrary to conotoxin PnIA or PnIB that are more selective.
 
Details
AA sequence:
 
Ile-Arg-Asp-Gla-Cys5-Cys6-Ser-Asn-Pro-Ala-Cys11-Arg-Val-Asn-Asn-Hyp-His-Val-Cys19-OH
 
(Disulfide bonds between Cys5-Cys11, Cys6-Cys19 )
Length (aa):
 
19
Formula:
C84H135N31O30S4
Molecular Weight:
 
2185.45 Da
Modifications
 
Gla4 amino acid (gamma-carboxyglutamic acid) and Hyp16 amino acid (Hydroxyproline)
Appearance:
 
White lyophilized solid
Solubility:
 
Water and saline buffer
CAS number:
Not available
Source:
 
Synthetic
Purity rate:
 
> 98 %
 
References
1. Banerjee J., et al. (2014)  Design and synthesis of α-conotoxin GID analogues as selective α4β2 nicotinic
   acetylcholine receptor antagonists. Biopolymers. PubMed link
2. Millard E., et al. (2009)  Inhibition of Neuronal Nicotinic  Acetylcholine Receptor Subtypes by  α-Conotoxin GID and
   Analogues. JBC. PubMed link
3. Nicke A., et al. (2003)  Isolation, Structure, and Activity of GID, a Novel 4/7-Conotoxin with an Extended N-terminal
   Sequence. JBC. PubMed link
 
 
Ordering informations

Catalog No.
Product Name
Size
13HTX003
Hainatoxin III
0.1 mg, 0.5 mg & 1.0 mg
13CON017
α-conotoxin PeIA
 0.1 mg, 5 x 0.1 mg & 0.5 mg
SAT001
TMR-ShK
0.1 mg
CON020
µ-conotoxin GIIIB
0.1 mg, 5 x 0.1 mg, 0.5 mg & 1 mg
CON019
α-conotoxin GID
0.1 mg, 5 x 0.1 mg, 0.5 mg & 1 mg
* 다른 사이즈나 bulk 공급도 가능하오니 별도로 문의하여 주십시오.

 
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