Peptide Series Peptide Synthetic Ion Channel Blockers for Research Peptides International has increased its portfolio of rich peptides which have potential therapeutic value, becoming the industry leader in this area. Many of these peptides originate from the of animals such as scor- pions, , snakes, sea anemones and cone snails, in which they act synergistically to immobilize prey or prevent predation. Several interesting drugs actually have originated from peptides such as Prialt () for the treatment of chronic intractable pain, which comes from Conus magus, and Integrillin (Eptifibatide), derived from venom from the rattlesnake Sistrurus miliarus barbbouri, which is an anticoagulant peptide. More recently, one of our research programs centered around the sea anemone peptide ShK (dalazatide), originating from Stichodactyla helianthus, for treating autoimmune diseases, has passed a phase 1b clinical trial. Therefore, we are delighted to offer a plethora of new disulfide rich peptides to facilitate your research/drug discovery programs. Our new products include three blocking peptides isolated from different venoms, Iberiotoxin, HsTX-1, and Martentoxin-1; Gurmarin, derived from the Gymnema sylvestre, which is a sweet-taste inhibiting peptide; and Tylotoin a wound healing peptide isolated from the skin of the salamander Tylototriton verrucosus. CODE PRODUCT QTY

GUR-3810-PI Gurmarin 1 mg Pyr-Gln-Cys-Val-Lys-Lys-Asp-Glu-Leu-Cys-Ile-Pro-Tyr-Tyr-Leu-Asp-Cys-Cys- 5 mg NEW! Glu-Pro-Leu-Glu-Cys-Lys-Lys-Val-Asn-Trp-Trp-Asp-His-Lys-Cys-Ile-Gly-OH

(M.W. 4208.95) C187H276N46O53S6 [138464-10-5] J.I. Fletcher, et al., Eur. J. Biochem., 264, 525 (1999). Y. Ninomiya, et al., Am J Physiol., 274, R1324 (1998). M. Sigoillot, et al., Appl. Microbiol. Biotechnol., 96, 619 (2012). A. Shiyovich, et al., Am. J. Med. Sci., 340, 514 (2010).

THS-3822-PI HsTX-1 1 mg H-Ala-Ser-Cys-Arg-Thr-Pro-Lys-Asp-Cys-Ala-Asp-Pro-Cys-Arg-Lys-Glu-Thr-Gly- 5 mg NEW! Cys-Pro-Tyr-Gly-Lys-Cys-Met-Asn-Arg-Lys-Cys-Lys-Cys-Asn-Arg-Cys-NH2

(M.W. 3818.53) C149H246N54O46S9 Disulfide bonds between C3-C24, C9-C29, C13-C31, and C19-C34 50 Kv1.3 channel blocker (IC ~ 12pM) PIB-3813-PI Iberiotoxin 1 mg IbTX 5 mg NEW! Pyr-Phe-Thr-Asp-Val-Asp-Cys-Ser-Val-Ser-Lys-Glu-Cys-Trp-Ser-Val-Cys-Lys-Asp-Leu-Phe-Gly-Val-Asp-Arg-Gly-Lys- Cys-Met-Gly-Lys-Lys-Cys-Arg-Cys-Tyr-Gln-OH

(M.W. 4230.8) C179H274N50O55S7 [129203-60-7] A. Galvez, et al., J. Biol. Chem., 265, 11083 (1990). (Original) K.M. Giangiacomo, et al., Biochemistry, 31, 6719 (1992). (Pharmacol.) M.L. Garcia, et al., J. Bioenerg. Biomembr., 23, 615 (1991). G. J. Kaczorowski, et al., J. Bioenerg. Biomembr., 28, 255 (1996). (Review) (Review) MAR-3811-PI Martentoxin-1 1 mg H-Gly-Leu-Ile-Asp-Val-Lys-Cys-Phe-Ala-Ser-Ser-Glu-Cys-Trp-Thr-Ala-Cys-Lys-Lys-Val-Thr- 5 mg NEW! Gly-Ser-Gly-Gln-Gly-Lys-Cys-Gln-Asn-Asn-Gln-Cys-Arg-Cys-Tyr-OH

(M.W. 3911.50) C162H253N49O52S6 Disulfide bonds between Cys8-Cys29, Cys14-Cys34, and Cys18-Cys36 Calcium-activated K+ channel inhibitor J. Tao, et al., PLOS one, 6e, 15896 (2011). J. Shi, et al., Biophy. Journal., 94, 3706 (2008). Y. Ji, et al., J. Neurochem., 84, 325 (2003). Z. Cao, et al., J. Peptides Res., 62, 252 (2003).

TYL-3814-PI Tylotoin 1 mg Salamander (Tylototriton verrucosus) 5 mg NEW! H-Lys-(Cys-Val-Arg-Gln-Asn-Asn-Lys-Arg-Val-Cys)-Lys-OH

(M.W. 1473.80) C59H108N24O16S2 Potential Wound Healing Peptide, Found in Salamander (Tylototriton verrucosus) Skin. Enhances Keratinocyte, Fibroblast and Vascular Endothelial Proliferation and Migration.

Peptides International, Inc. P.O. Box 99703 Phone: 502-266-8787 1-800-777-4779 Louisville, KY 40269-0703 USA Fax: 502-267-1329 E-mail: [email protected] 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.

CODE COMPOUND QTY CODE COMPOUND QTY

PAG-4256-s ω-Agatoxin-IVA 0.1 mg vial PCB-4455-s -IV 0.1 mg vial NEW!

PAG-4294-s ω-Agatoxin TK 0.1 mg vial PIB-4235-s Iberiotoxin (IbTX) 0.1 mg vial

PAG-4247-s Agelenin 0.1 mg vial PIM-4343-s Imperatoxin A (IpTXa) 0.1 mg vial

PAP-4257-v Apamin 0.5 mg vial PKL-4259-s Kaliotoxin (1-37) 0.1 mg vial

PAG-3402-s Biotinyl-ω-Agatoxin IVA 0.1 mg vial PKT-4375-s Kurtoxin 0.1 mg vial NEW! PCC-4310-s 0.1 mg vial MAM-3778-PI Mambalgin-1 0.5 & 1 mg NEW! PCL-4255-s 0.1 mg vial PAR-4290-s (MGTX) 0.1 mg vial

PCB-4227-s (ChTX) 0.1 mg vial MAR-3811-PI Martentoxin-1 1 & 5 mg NEW!

PCN-4282-v Chlorotoxin 0.5 mg vial PMC-4258-v Mast Cell Degranulating Peptide 0.5 mg vial

PCN-4126-v α- GI 0.5 mg vial PMS-4107-v Mastoparan 0.5 mg vial

PCN-4140-v α-Conotoxin MI 0.5 mg vial PMT-4341-s Muscarinic Toxin 1 (MTX1, MT1) 0.1 mg vial

PCN-4311-v α-Conotoxin ImI 0.5 mg vial PMT-4410-s Muscarinic Toxin 3 0.1 mg vial (MT3, MTX3, m4-toxin) PCN-4228-v α-Conotoxin SI 0.5 mg vial PMT-4340-s Muscarinic Toxin 7 (MTX7, MT7) 0.1 mg vial PCN-4263-v µ-Conotoxin GS 0.5 mg vial PNT-4195-s , NSTX-3 0.1 mg vial PCN-4217-v µ-Conotoxin GIIIB 0.5 mg vial PPL-4300-s PLTX-II 0.1 mg vial PCN-4440-v µ-Conotoxin SIIIA 0.5 mg vial NEW! PTX-4409-s ProTx-I 0.1 mg vial PCN-4161-v ω-Conotoxin GVIA 0.5 mg vial PTX-4450-s ProTx-II 0.1 mg vial PCN-4283-s ω-Conotoxin MVIIC 0.1 mg vial PTX-4435-s 1 0.1 mg vial PCN-4283-v ω-Conotoxin MVIIC 0.5 mg vial PSF-4206-s Sarafotoxin S6b 0.1 mg vial PCN-4289-v ω-Conotoxin MVIIA 0.5 mg vial PPT-4457-s Purotoxin-1 0.1 mg vial PCN-4284-v ω-Conotoxin SVIB 0.5 mg vial PSF-4246-s Sarafotoxin S6c 0.1 mg vial PDN-4330-s I 0.1 mg vial PCB-4363-s SNX-482 0.1 mg vial ECT-3760-PI Echistatin 1 & 5 mg NEW! PSC-4260-s /Leiurotoxin 0.1 mg vial ENT-3744-PI STp 1 & 5 mg NEW! PSK-4287-s Stichodactyla Toxin 0.1 mg vial SHK-3746-PI 5-Fam-ShK 1 & 5 mg NEW! PTK-4364-s Tertiapin 0.1 mg vial TGX-3862-PI GpTx-1 1 & 5 mg NEW! PTT-4313-s Tityustoxin Kα 0.1 mg vial GUR-3810-PI Gurmarin 1 & 5 mg TYL-3814-PI Tylotoin 1 & 5 mg NEW! PGX-4433-s Guangxitoxin-1E 0.1 mg vial PUG-3772-PI Uroguanylin (Human) 1 & 5 mg NEW! NEW! THS-3822-PI HsTX-1 1 & 5 mg PUG-4295-s Uroguanylin Isomer A (Human) 0.1 mg vial NEW!

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

PLEASE NOTE: Conotoxin peptides are not available for export without a license from the US Department of Commerce. To place an order for conotoxin peptides to be shipped within the United States please contact Peptides International to obtain important information regarding the CDC Select Agent Transfer Program. Thank you for your cooperation! Some Products of Interest from the Peptide Institute CODE PRODUCT QTY

PMT-4410-s Muscarinic Toxin 3 0.1 mg (Green , Dendroaspis angusticeps) vial MT3, MTX3, m4-toxin Synthetic Product Leu-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 -4 (M4) M. Jolkkonen, et al., FEBS Lett., 352, 91 (1994). (Original; MT3) J.-S. Liang, et al., Toxicon, 34, 1257 (1996). (Original; m4-toxin) A. Adem and E. Karlsson, Life Sci., 60, 1069 (1997). (Pharmacol.; Muscarinic Receptor Subtype Specificity) S. Katayama, et al., Peptide Science 2004, 161 (2005). (S-S Bond)

PTX-4409-s ProTx-I 0.1 mg vial Synthetic 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 ) C171H245N53O47S6 T-Type Ca2+ Channel / Na+ Channel / K+ Channel Blocker (Gating Modifier)

PTX-4450-s ProTx-II 0.1 mg vial Synthetic 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 + 2+ Na Channel (Especially Nav1.7) / Ca Channel Blocker (Gating Modifier) PTX-4435-s Psalmotoxin 1 0.1 mg vial Selective Blocker for Acid-Sensitive Ion Channel, ASIC1a

PTX-4450-s μ-SLPTX-Ssm6a 0.5 mg Synthetic Product 1 mg (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 + 2+ Na Channel (Especially Nav1.7) / Ca Channel Blocker (Gating Modifier)

Peptides International, known as the disulfide-rich peptide specialists, is proud to announce the

NEW! addition of a new product line to its broad offerings, a collection of new synthetic venom libraries, 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 draw- backs to venom-derived peptides. These include: the components are often hidden and inac- cessible, 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 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 for more information. DML-8000 δ-melusine™ - Collection I PRICE: delta-Melusine™ - Synthetic venom libraries. Inquire for pricing, as each library’s pricing is based on range INQUIRE and quantity. Options include: public domain sequences, proprietary natural sequences, and unique sequenc- es designed in-house. TYPE CODE PRODUCT QTY TYPE CODE PRODUCT QTY L-type PCL-4255-s Calciseptine 0.1 mg vial PMC-4258-v Mast Cell Degranulating 0.5 mg vial L-type PCC-4310-s Calcicludine (CaC) 0.1 mg vial (MCD) Peptide

N-type PCN-4161-v ω-Conotoxin GVIA 0.5 mg vial PSK-4287-s Stichodactyla Toxin (ShK) 0.1 mg vial

N-type PCN-4289-v ω-Conotoxin MVIIA 0.5 mg vial SHK-3770-PI Stichodactyla Toxin Amide 1 mg 5 mg N-type PCN-4284-v ω-Conotoxin SVIB 0.5 mg vial Channel Blockers + PAR-4290-s Margatoxin (MgTX) 0.1 mg vial P-type PAG-4256-s ω-Agatoxin IVA 0.1 mg vial PTT-4313-s Tityustoxin Kα (TsTX-K ) 0.1 mg vial P-type PAG-4294-s ω-Agatoxin TK 0.1 mg vial PDN-4330-s Dendrotoxin I 0.1 mg vial P/Q-type PCN-4283-s ω-Conotoxin MVIIC 0.1 mg vial PTX-4409-s ProTx-I 0.1 mg vial P/Q-type PCN-4283-v ω-Conotoxin MVIIC 0.5 mg vial

Voltage Dependent K Voltage PGX-4433-s Guangxitoxin-1E 0.1 mg vial R-type PCB-4363-s SNX-482 0.1 mg vial PCN-4217-v µ-Conotoxin GIIIB 0.5 mg vial T-type PKT-4375-s Kurtoxin 0.1 mg vial PCN-4263-v µ-Conotoxin GS 0.5 mg vial PPL-4300-s PLTX-II 0.1 mg vial Channel Blockers PCB-4455-s Huwentoxin 0.1 mg vial 2+ T-type PTX-4409-s ProTx-I 0.1 mg vial Ca PTX-4409-s ProTx-I 0.1 mg vial T-type PTX-4450-s ProTx-II 0.1 mg vial PTX-4450-s ProTx-II 0.1 mg vial

2+ + Channel Blockers Ca Activated K Channel Blockers +

Na PTX-4435-s Psalmotoxin 1 0.1 mg vial BK-type1 PIB-4235-s Iberiotoxin (IbTX) 0.1 mg vial PCN-4282-v Chlorotoxin 0.5 mg vial BK-type1 PIB-3813-PI Iberiotoxin (IbTX) (bulk) 1 mg 5 mg Channel BK-type1 PKL-4259-s Kaliotoxin (1-37) 0.1 mg vial - Cl Blocker

MAR-3811-PI Martentoxin 1 mg All Peptides International -s and -v products are sold with net peptide weight content 5 mg and solubility data is provided for each lot. 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 2 3 Channel Blocker High Conductance; Intermediate Conductance; Small Conductance +

K *also has BK-type blocking activity

Peptides International, Inc. P.O. Box 99703 Phone: 502-266-8787 1-800-777-4779 Louisville, KY 40269-0703 USA Fax: 502-267-1329 E-mail: [email protected]