1-800-777-4779 E-mail: peptides@pepnet.com

Phone: 502-266-8787 Fax: 502-267-1329

P.O. Box 99703Louisville, KY 40269-0703 USA

Peptides International, Inc.

Peptide Toxin Series

Peptide Toxins

ProTx-II, like its predecessor ProTx-I, was also isolated and characterized from the venom of tarantula Thrixopelma pruriens.1-3 Along with ProTx-I, these

peptide toxins belong to the inhibitory cystine knot (ICK) family, which is known to interact with voltage-gated ion channels. They are unique because they alter the rate of activation and not inactivation of channels. Otherwise, there is no sequence homology between ProTx-I and -II. It was shown to be at least 100-fold selective for Nav1.7 channel with an IC50 of 0.3 nM.4 Sodium channel subtype Nav1.7 has a role in modulating neuronal signaling for pain, and recent studies indicate loss-of-function mutations in Nav1.7 cause insensitivity to pain.5 Others have identified gain-of-function mutations in Nav1.7 as the cause to certain pain disorders.6-8 Thus Nav1.7 is a potential target for the development of analgesics.

The highly sensitive nature of ProTx-II for Nav1.7 is believed to be due to the presence of a unique phenylalanine residue (F813) present in the C-terminal domain II S3 of the channel, which makes it different than the other sodium channel subtypes. Indeed, mutation of the F813 to glycine or serine reduced the sensitivity of ProTx-II significantly.4

Evidence indicates the ProTx-II may not be able to cross the blood-nerve barrier since intravenous administration in rats did not significantly block acute pain response. In addition, the toxin can block C-fiber action potential propagation in

desheathed but not intact nerves.4 While this may limit the use of ProTx-II, the toxin should still act

as an important tool for locating novel inhibitors for Nav1.7.Peptides International has now added another offering to its “menagerie” of peptide toxins with exciting implications for pain management drug discovery. μ-SLPTX-Ssm6a, derived from the Chinese redheaded centipede (Scolopendra subspinipes mutilans), is a 46-residue, 3 disulfide peptide which is selective for Nav1.7, currently a target of great interest for pain management. Interestingly, its analgesic efficacy has been found to exceed that of morphine in rodent pain models.9

This peptide toxin has no homology to any previously reported Nav1.7 blockers such as ProTx-II. This makes it a very novel toxin to add to the researcher’s toolbox and as a promising drug-discovery aid Peptides International believes this product “has

legs”!

1. R.E. Middleton, et al., Biochemistry, 41, 14734 (2002). (Original) 2. B.T. Priest, et al., Toxicon, 49, 194 (2007). (Review) 3. J.J. Smith, et al., J. Biol. Chem., 282,12687 (2007). (Pharmacol.; Novel Toxin Binding Site Coupled to NaV Activation)4. W.A. Schmalhofer,et al., Mol. Pharmacol., 74,1476 (2008).

5. S.D. Dib-Hajj, et al., Trends Neurosci, 30, 555 (2007).6. C.R. Fertleman, et al., Neuron, 52, 767 (2006).7. C. Han, et al., Ann Neurol., 59, 553 (2006). 8. Y. Yang, et al., Journal of Med. Genetics, 41171 (2004).9. S. Yang, , et al., published online before print 9-30- 2013, doi:10.1073/pnas.1306285110

CODE PRODUCT QTY

PTX-4450-s μ-SLPTX-Ssm6aSynthetic Product (Centipede, Scolopendra subspinipes mutilans)H-Ala-Asp-Asn-Lys-Cys-Glu-Asn-Ser-Leu-Arg-Arg-Glu-Ile-Ala-Cys-Gly-Gln-Cys-Arg-Asp-Lys-Val-Lys-Thr- Asp-Gly-Tyr-Phe-Tyr-Glu-Cys-Cys-Thr-Ser-Asp-Ser-Thr-Phe-Lys-Lys-Cys-Gln-Asp-Leu-Leu-His-OH (Folded to the most thermodynamically stable isomer) C221H344N66O75S6 5317.99 Na+ Channel (Especially Nav1.7) / Ca2+ Channel Blocker (Gating Modifier)

0.5 mg 1 mg

PTX-4450-s ProTx-IISynthetic Product (Tarantula, Thrixopelma pruriens)Tyr-Cys-Gln-Lys-Trp-Met-Trp-Thr-Cys-Asp-Ser-Glu-Arg-Lys-Cys-Cys-Glu-Gly-Met-Val-Cys-Arg-Leu-Trp-Cys-Lys-Lys-Lys-Leu-Trp(Disulfide bonds between Cys2-Cys16, Cys9- Cys21, and Cys15-Cys25) (M.W. 3826.60) C168H250N46O41S8 Na+ Channel (Especially Nav1.7) / Ca2+ Channel Blocker (Gating Modifier)

0.1 mg vial

Synthetic Ion Channel Blockers for Pain ResearchSee inside for MANY NEW! items

PEPTIDE TOXINS - A QUICK REFERENCE(see back page for channel blockers and gating modifiers)

All Peptides International -s and -v products are sold with net peptide weight. Content and solubility data is provided for each lot.

ProTx-I peptide was first isolated and characterized from the venom of tarantula Thrixopelma pruriens and consists of 35 amino acids.1 This peptide toxin belongs to the inhibitory cystine knot (ICK) family, which is known to

interact with voltage-gated ion channels. ProTx-I does not effect the rate of inactivation of channels but modifies the conformation of channels to an open position by shifting voltage dependence to more positive potentials. In addition, this toxin, like other members of the ICK family of spider toxins, can bind multiple voltage-gated ion channel families. ProTx-I inhibits: 1) T-type Ca2+ channel, Cav 3.1 by 84%; 2) Na+ channels, Nav1.2, Nav1.5, Nav1.7, and Nav1.8 by about 80%; and 3) K+ channels, Kv2.1 by 60% and

Kv1.3 by 40%. ProTx-I elicits multiple channel blocking activities with certain selectivity, since K+ channel inhibitory activity is relatively weak. This is one of the first high affinity ligands reported for tetrodotoxin-resistant Na+ and T-type Ca2+ channels. These ion channels can play a role in secretion of hormones and neurotransmitters and contribute to cardiovascular and neuropsychiatric disorders. For example, neuronal T-type Ca2+ channels can contribute to changes in oscillation in the thalamus cells.2 Oscillatory changes have been associated with tremor of Parkinson’s disease, tinnitus, neuropsychiatric disorders like schizophrenia, and neurogenic pain. In addition, Ca2+ channels have been implicated as the pace maker current in the

CODE COMPOUND QTY

PGX-4433-s Guangxitoxin-1E 0.1 mg vial

PCB-4455-s Huwentoxin-IV 0.1 mg vial

PIB-4235-s Iberiotoxin (IbTX) 0.1 mg vial

PIM-4343-s Imperatoxin A (IpTXa) 0.1 mg vial

PKL-4259-s Kaliotoxin (1-37) 0.1 mg vial

PKT-4375-s Kurtoxin 0.1 mg vial

MAM-3778-PI Mambalgin-1 0.5 & 1 mg

PAR-4290-s Margatoxin (MGTX) 0.1 mg vial

PMC-4258-v Mast Cell Degranulating Peptide 0.5 mg vial

PMS-4107-v Mastoparan 0.5 mg vial

PMT-4341-s Muscarinic Toxin 1 (MTX1, MT1) 0.1 mg vial

PMT-4410-s Muscarinic Toxin 3 (MT3, MTX3, m4-toxin)

0.1 mg vial

PMT-4340-s Muscarinic Toxin 7 (MTX7, MT7) 0.1 mg vial

PNT-4195-s Neurotoxin, NSTX-3 0.1 mg vial

PPL-4300-s PLTX-II 0.1 mg vial

PTX-4409-s ProTx-I 0.1 mg vial

PTX-4450-s ProTx-II 0.1 mg vial

PTX-4435-s Psalmotoxin 1 0.1 mg vial

PSF-4206-s Sarafotoxin S6b 0.1 mg vial

PPT-4457-s Purotoxin-1 0.1 mg vial

PSF-4246-s Sarafotoxin S6c 0.1 mg vial

PCB-4363-s SNX-482 0.1 mg vial

PSC-4260-s Scyllatoxin/Leiurotoxin 0.1 mg vial

PSK-4287-s Stichodactyla Toxin 0.1 mg vial

PTK-4364-s Tertiapin 0.1 mg vial

PTT-4313-s Tityustoxin Kα 0.1 mg vial

PUG-3772-PI Uroguanylin (Human) 1 & 5 mg

PUG-4295-s Uroguanylin Isomer A (Human) 0.1 mg vial

PUG-4463-s Uroguanylin Isomer B (Human) 0.1 mg vial

CODE COMPOUND QTY

STX-3791-PI μ-SLPTX-Ssm6a EXCLUSIVE CATALOG OFFERING!

0.5 & 1 mg

PAG-4256-s ω-Agatoxin-IVA 0.1 mg vial

PAG-4294-s ω-Agatoxin TK 0.1 mg vial

PAG-4247-s Agelenin 0.1 mg vial

PAP-4257-v Apamin 0.5 mg vial

PAG-3402-s Biotinyl-ω-Agatoxin IVA 0.1 mg vial

PCC-4310-s Calcicludine 0.1 mg vial

PCL-4255-s Calciseptine 0.1 mg vial

PCB-4227-s Charybdotoxin (ChTX) 0.1 mg vial

PCN-4282-v Chlorotoxin 0.5 mg vial

PCN-4126-v α-Conotoxin GI 0.5 mg vial

PCN-4140-v α-Conotoxin MI 0.5 mg vial

PCN-4311-v α-Conotoxin ImI 0.5 mg vial

PCN-4228-v α-Conotoxin SI 0.5 mg vial

PCN-4263-v µ-Conotoxin GS 0.5 mg vial

PCN-4217-v µ-Conotoxin GIIIB 0.5 mg vial

PCN-4440-v µ-Conotoxin SIIIA 0.5 mg vial

PCN-4161-v ω-Conotoxin GVIA 0.5 mg vial

PCN-4283-s ω-Conotoxin MVIIC 0.1 mg vial

PCN-4283-v ω-Conotoxin MVIIC 0.5 mg vial

PCN-4289-v ω-Conotoxin MVIIA 0.5 mg vial

PCN-4284-v ω-Conotoxin SVIB 0.5 mg vial

PDN-4330-s Dendrotoxin I 0.1 mg vial

ECT-3760-PI Echistatin 1 & 5 mg

ENT-3744-PI Enterotoxin STp 1 & 5 mg

SHK-3746-PI 5-Fam-ShK 1 & 5 mg

PLEASE NOTE: Conotoxin peptides are not available for export without a li-cense from the US Department of Commerce. To place an order for conotoxin peptides to be shipped within the United States please contact Peptides Interna-tional to obtain important information regarding the CDC Select Agent Transfer Program. Thank you for your cooperation!

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CODE PRODUCT QTY

PTX-4409-s ProTx-ISynthetic Product(Tarantula, Thrixopelma pruriens)Glu-Cys-Arg-Tyr-Trp-Leu-Gly-Gly-Cys-Ser-Ala-Gly-Gln-Thr-Cys-Cys-Lys-His-Leu-Val-Cys-Ser-Arg-Arg-His-Gly-Trp-Cys-Val-Trp-Asp-Gly-Thr-Phe-Ser(Disulfide bonds between Cys2-Cys16, Cys9-Cys21, and Cys15- Cys28)(M.W. 3987.50 ) C171H245N53O47S6T-Type Ca2+ Channel / Na+ Channel / K+ Channel Blocker (Gating Modifier)

0.1 mg vial

Muscarinic (M) receptors belong to the G-protein coupled receptor family and consist of 5 sub-types, M1-M5, that are activated by acetylcho-line (ACh). The M4 receptor is present primar-

ily on neurons in the central nervous system of mammals; therefore, it is not surprising that recent studies implicate a role for the receptor in memory, learning, psychosis, motor control, and metabolism. Several studies have found that M4 receptors were significantly reduced in dentate gyrus in Alzheimer’s patients, and receptor binding was associated with impaired consciousness and visual hallucinations in Alzheimer’s patients.1,2 Behavior studies indicate M4 plays a role in regulation of movement and prepulse inhibition of startle reflex, a measure of attention.3 Others have shown that injection of muscarinic toxin 3 (MT3), a M4 receptor antagonist, in rat hippocampus caused amnesia in those animals.4

Evidence suggests that M4 receptors also participate in the inhibitory control of dopamine 1 (D1) receptors. Both re-

ceptors can be found in striatonigral neurons.5 M4 deficient mice have elevated basal locomotive activity and increased locomotive response following activation of D1 receptors.6,7 Loss of dopamine regulation has been associated with dis-eases such as Parkinson’s and Schizophrenia. In addition, mounting evidence suggests muscarinic receptors may have a metabolic role in insulin control. Pretreatment of clonal beta cells with M4 antagonist, MT3, increased ACh-induced insulin secretion by as much as 168%.8

MT3 is a three finger toxin that consists of 65 amino acids and 4 disulfide bonds. It was first isolated from Green Mamba venom and was shown to be highly selective for M4 receptor in assays done in CHO cells cloned with hu-man M1-M4 and neuroblastoma cells expressing M4.9,10,11 Peptides International currently offers this new, potent selective M4 receptor antagonist for research applications. MT3 (PMT-4410-s) should provide a valuable tool for inves-tigating the role of this receptor in functional responses and related diseases such as Parkinson’s and Alzheimer’s.

CODE PRODUCT QTY

PMT-4410-s Muscarinic Toxin 3(Green Mamba, Dendroaspis angusticeps)MT3, MTX3, m4-toxinSynthetic ProductLeu-Thr-Cys-Val-Thr-Lys-Asn-Thr-Ile-Phe-Gly-Ile-Thr-Thr-Glu-Asn-Cys-Pro-Ala-Gly-Gln-Asn-Leu-Cys-Phe-Lys-Arg-Trp-His-Tyr-Val-Ile-Pro-Arg-Tyr-Thr-Glu-Ile-Thr-Arg-Gly-Cys-Ala-Ala-Thr-Cys-Pro-Ile-Pro-Glu-Asn-Tyr-Asp-Ser-Ile-His-Cys-Cys-Lys-Thr-Asp-Lys-Cys-Asn-Glu(Disulfide bonds between Cys3- Cys24, Cys17- Cys42, Cys46- Cys57, and Cys58- Cys63)(M.W. 7379.40 ) C319H489N89O97S8 Specific Ligand for Muscarinic Acetylcholine Receptor-4 (M4)M. Jolkkonen, P.L.M. van Giersbergen, U. Hellman, C. Wernstedt, and E. Karlsson, FEBS Lett., 352, 91 (1994). (Original; MT3) J.-S. Liang, J. Carsi-Gabrenas, J.L. Krajewski, J.M. McCafferty, S.L. Purkerson, M.P. Santiago, W.L. Strauss, H.H. Valentine, and L.T. Potter, Toxicon, 34, 1257 (1996). (Original; m4-toxin) A. Adem and E. Karlsson, Life Sci., 60, 1069 (1997). (Pharmacol.; Muscarinic Receptor Subtype Specificity)S. Katayama, M. Ishimaru, H. Nishio, Y. Nishiuchi, and T. Kimura, Peptide Science 2004, 161 (2005). (S-S Bond)

0.1 mgvial

1. E. Mulugeta, E. Karlsson, A. Islam, R. Kalaria, H. Mangat, B. Winblad, and A. Adem. Brain Res., 960, 259 (2003). 2. T. Teaktong, M.A. Piggott, I.G. Mckeith, R.H. Perry, C.G. Ballard, and E.K. Perry. Behav. Brain Res., 161, 299 (2005). 3. C.C. Felder, A.C. Porter, T.L. Skillman, L. Zhang, F.P. Bymaster, N.M. Nathanson, S.E. Hamilton, J. Gomeza, J. Wess, and D.L. McKinzie. Life Sci., 68, 2605 (2001). 4. D. Jerusalinsky, E. Kornisiuk, P. Alfaro, J. Quillfeldt, M. Alonso, E.R. Verde, C. Cervenansky, and A Harvey. Neuroreport, 9, 1407 (1998). 5. E. Ince, B.J. Ciliax, and A.I. Levey. Synapse, 27, 357 (1997). 6. J. Gomeza, L. Zhang, E. Kostenis, C.C. Felder, F.P. Bymaster, J. Brodkin, H. Shannon, B. Xia, A. Duttaroy, C.X. Deng, and J. Wess. Life Sci., 68, 2457 (2001). 7. J. Gomeza, L. Zhang, E. Kostenis, C. Felder, F. Bymaster, J. Brodkin, H. Shannon, B. Xia, C. Deng, and J. Wess. Neurobiology, 96, 10483 (1999). 8. J.C. Miguel, Y.H. Abdel-Wahab, P.C. Mathias, and P.R. Flatt. Biochem Biophys. Acta., 1569, 45 (2002). 9. E. Karlsson, M. Jolkkonen, N. Satypan, A. Adem, E. Kumlin, U. Hellman, and C. Wernstedt, Ann. NY Acad. Sci., 710, 153 (1994).10. M. Jolkkonen, P.L. van Giersbergen, U. Hellman, C. Wernstedt, and E. Karlsson. FEBS Lett., 352, 91 (1994).11. M.C. Olianas, A. Ingianni, C. Maullu, A. Adem, E. Karlsson, and P. Onali., J. Pharmacol. Exp. Ther., 288, 164 (1999).

1. R.E. Middleton, V.A. Warren, R.L. Kraus, J.C. Hwang, C.J. Liu, G. Dai, R.M. Brochu, M.G. Kohler, Y.D. Gao, V.M. Garsky, M.J. Bogusky, J.T. Mehl, C.J. Cohen, and M.M. Smith, Biochemistry, 41, 14734 (2002). (Original)

2. J.R. Huguenard and D.A Prince, J. Neurosc., 14, 5485 (1994).3. S. Fareh, A. Benardeau, B. Thibault, and S. Natte, Circulation, 100, 2191 (1999).4. S. Fareh, A. Benardeau, and S. Nattel, Cardiovascular Res., 4, 762 (2001).

References

heart and suggested in previous studies to participate in atrial remodeling.3,4 ProTx-I peptide should assist in the

understanding of the role of voltage-gated ion channels in physiology and disease.

1-800-777-4779 E-mail: peptides@pepnet.com

Phone: 502-266-8787 Fax: 502-267-1329

P.O. Box 99703Louisville, KY 40269-0703 USA

Peptides International, Inc.

TYPE CODE PRODUCT QTYCa

2+ C

hann

el Bl

ocke

rs

L-type PCL-4255-s Calciseptine 0.1 mg vial

L-type PCC-4310-s Calcicludine (CaC) 0.1 mg vial

N-type PCN-4161-v ω-Conotoxin GVIA 0.5 mg vial

N-type PCN-4289-v ω-Conotoxin MVIIA 0.5 mg vial

N-type PCN-4284-v ω-Conotoxin SVIB 0.5 mg vial

P-type PAG-4256-s ω-Agatoxin IVA 0.1 mg vial

P-type PAG-4294-s ω-Agatoxin TK 0.1 mg vial

P/Q-type PCN-4283-s ω-Conotoxin MVIIC 0.1 mg vial

P/Q-type PCN-4283-v ω-Conotoxin MVIIC 0.5 mg vial

R-type PCB-4363-s SNX-482 0.1 mg vial

T-type PKT-4375-s Kurtoxin 0.1 mg vial

PPL-4300-s PLTX-II 0.1 mg vial

T-type PTX-4409-s ProTx-I 0.1 mg vial

T-type PTX-4450-s ProTx-II 0.1 mg vial

K+ Cha

nnel

Bloc

ker

Ca2+ Activated K+ Channel Blockers

BK-type1 PIB-4235-s Iberiotoxin (IbTX) 0.1 mg vial

BK-type1 PKL-4259-s Kaliotoxin (1-37) 0.1 mg vial

IK-type2 PCB-4227-s Charybdotoxin* (ChTX) 0.1 mg vial

SK-type3 PAP-4257-v Apamin 0.5 mg vial

SK-type3 PSC-4260-s Scyllatoxin (Leiurotoxin I) 0.1 mg vial

1 High Conductance; 2 Intermediate Conductance; 3 Small Conductance *also has BK-type blocking activity

TYPE CODE PRODUCT QTY

Volta

ge D

epen

dent

K+ Cha

nnel

Bloc

kers

PMC-4258-v Mast Cell Degranulating (MCD) Peptide

0.5 mg vial

PSK-4287-s Stichodactyla Toxin (ShK) 0.1 mg vial

SHK-3770-PI Stichodactyla Toxin Amide 1 mg 5 mg

PAR-4290-s Margatoxin (MgTX) 0.1 mg vial

PTT-4313-s Tityustoxin Kα (TsTX-K ) 0.1 mg vial

PDN-4330-s Dendrotoxin I 0.1 mg vial

PTX-4409-s ProTx-I 0.1 mg vial

PGX-4433-s Guangxitoxin-1E 0.1 mg vial

Na+ C

hann

el B

locke

rs

PCN-4217-v µ-Conotoxin GIIIB 0.5 mg vial

PCN-4263-v µ-Conotoxin GS 0.5 mg vial

PCB-4455-s Huwentoxin 0.1 mg vial

PTX-4409-s ProTx-I 0.1 mg vial

PTX-4450-s ProTx-II 0.1 mg vial

PTX-4435-s Psalmotoxin 1 0.1 mg vial

STX-3791-PI μ-SLPTX-Ssm6a EXCLUSIVE CATALOG OFFERING

0.5 mg 1 mg

Cl-

Chan

nel

Bloc

ker PCN-4282-v Chlorotoxin 0.5 mg vial

All Peptides International -s and -v products are sold with net peptide weight content and solubility data is provided for each lot.

Peptides International, known as the disulfide-rich peptide specialists, is proud to announce the addition of a new product line to its broad offerings, a collection of new synthetic venom librar-ies, which includes these features:

public domain sequences • proprietary natural sequences • unique sequences designed in-house

Peptide toxins have been a promising area of drug discovery the last few years, but there are drawbacks to venom-derived peptides. These include: the components are often hidden and inaccessible, most species are too small for venom production, are extremely rare and hard to

collect. δ-melusine™, produced by Atheris Laboratories of Switzerland, circumvents all of these issues. Sequences are designed around structural scaffolds, combined with data-mining, Reverse-Discovery™ and by clustering venoms into structural families.

The first kit available, Collection I, has a total of 658 spider neurotoxin peptides available - with more coming soon!

As the exclusive distributor of the δ-melusine™ product line in North America, Peptides International further strengthens its extensive disulfide-rich peptide portfolio, which includes hepcidins, the extremely popular Mambalgin-1, ShK peptides, defensins and toxins. This is augmented by industry-leading disulfide-rich peptide expertise combined with a comprehensive and friendly customer service. Please inquire here for more information.

NEW!

DML-8000 δ-melusine™ - Collection Idelta-Melusine™ - Synthetic venom libraries. Inquire for pricing, as each library’s pricing is based on range and quantity. Options include: public domain sequences, proprietary natural sequences, and unique sequences designed in-house.

PRICE: INQUIRE

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