MilliporeSigma
  • Home
  • Search Results
  • Studies examining the relationship between the chemical structure of protoxin II and its activity on voltage gated sodium channels.

Studies examining the relationship between the chemical structure of protoxin II and its activity on voltage gated sodium channels.

Journal of medicinal chemistry (2014-07-16)
Jae H Park, Kevin P Carlin, Gang Wu, Victor I Ilyin, Laszlo L Musza, Paul R Blake, Donald J Kyle
ABSTRACT

The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a well-defined inhibitor cystine knot (ICK) backbone region and a flexible C-terminal tail region, similar to previously described NaSpTx III tarantula toxins. In the present study we sought to explore the structure-activity relationship of the two regions of the ProTx II molecule. As a first step, chimeric toxins of ProTx II and PaTx I were synthesized and their biological activities on Nav1.7 and Nav1.2 channels were investigated. Other tail region modifications to this chimera explored the effects of tail length and tertiary structure on sodium channel activity. In addition, the activity of various C-terminal modifications of the native ProTx II was assayed and resulted in the identification of protoxin II-NHCH3, a molecule with greater potency against Nav1.7 channels (IC50=42 pM) than the original ProTx II.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phenol, BioXtra, ≥99.5% (GC)
Sigma-Aldrich
Phenol solution, Saturated with 0.1 M citrate buffer, pH 4.3 ± 0.2, BioReagent, for molecular biology
Sigma-Aldrich
Phenol solution, Equilibrated with 10 mM Tris HCl, pH 8.0, 1 mM EDTA, BioReagent, for molecular biology
Sigma-Aldrich
Acetonitrile, ≥99.5%, ACS reagent
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Phenol, contains hypophosphorous as stabilizer, loose crystals, ACS reagent, ≥99.0%
Sigma-Aldrich
N,N-Diisopropylethylamine, purified by redistillation, 99.5%
Sigma-Aldrich
Phenol, unstabilized, ReagentPlus®, ≥99%
Sigma-Aldrich
Phenol, for molecular biology
Sigma-Aldrich
Phenol, ≥99%
Supelco
Phenol solution, 100 μg/mL in acetonitrile, PESTANAL®, analytical standard
Sigma-Aldrich
Phenol, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Phenol, BioUltra, for molecular biology, TE-saturated, ~73% (T)
Sigma-Aldrich
N,N-Diisopropylethylamine, ReagentPlus®, ≥99%
Supelco
Acetonitrile, HPLC grade, ≥99.93%
Supelco
Acetonitrile, analytical standard
Supelco
Phenol, PESTANAL®, analytical standard
Sigma-Aldrich
Phenol, puriss., meets analytical specification of Ph. Eur., BP, USP, ≥99.5% (GC), crystalline (detached)
Sigma-Aldrich
Piperidine solution, suitable for peptide synthesis, 20% in DMF
Sigma-Aldrich
Phenol, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.5-100.5% (GC)
Sigma-Aldrich
Phenol, puriss. p.a., ACS reagent, reag. Ph. Eur., 99.0-100.5%
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Supelco
Phenol solution, 5000 μg/mL in methanol, certified reference material
Supelco
Phenol solution, certified reference material, 500 μg/mL in methanol
Supelco
Phenol, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
Sigma-Aldrich
Phenol, unstabilized, purified by redistillation, ≥99%