• Nanion Technologies: イオンチャネル研究のスマートツール

    Nanion Technologies: イオンチャネル研究のスマートツール

  • CardioExcyte 96 SOL: 心筋の光ペーシング

    CardioExcyte 96 SOL: 心筋の光ペーシング

  • SURFE²R 96SE: ラベルフリーのトランスポーターHTS

    SURFE²R 96SE: ラベルフリーのトランスポーターHTS

  • 脂質二分子膜実験: Orbitシリーズ

    脂質二分子膜実験: Orbitシリーズ

Our Product Portfolio

SyncroPatch 384i

SyncroPatch 384i

Patchliner

Patchliner

Port-a-Patch

Port-a-Patch

Port-a-Patch mini

Port-a-Patch mini

CardioExcyte 96

CardioExcyte 96

FLEXcyte 96

FLEXcyte 96

SURFE²R 96SE

SURFE²R 96SE

SURFE²R N1

SURFE²R N1

Orbit 16

Orbit 16

Orbit Mini

Orbit Mini

Vesicle Prep Pro

Vesicle Prep Pro

2017 - A mutant of the Buthus martensii Karsch antitumor-analgesic peptide exhibits reduced inhibition to hNav1.4 and hNav1.5 channels while retaining analgesic activity

icon pap   Port-a-Patch publication in Journal of Biological Chemistry (2017)

Authors:
Xu Y., Meng X., Hou X., Sun J., Kong X., Sun Y., Liu Z., Ma Y., Niu Y., Song Y., Cui Y., Zhao M., Zhang J.

 

Journal:
Journal of Biological Chemistry (2017) 292:18270-18280


Abstract:

Scorpion toxins can kill other animals by inducing paralysis and arrhythmia, which limits the potential applications of these agents in the clinical management of diseases. Antitumor-analgesic peptide (AGAP), purified from Buthus martensii Karsch, has been proved to possess analgesic and antitumor activities. Trp38, a conserved aromatic residue of AGAP, might play an important role in mediating AGAP activities according to the sequence and homology-modeling analyses. Therefore, an AGAP mutant, W38G, was generated, and effects of both AGAP and the mutant W38G were examined by whole-cell patch clamp techniques on the sodium channels hNaV1.4 and hNaV1.5, which were closely associated with the biotoxicity of skeletal and cardiac muscles, respectively. The data showed that both W38G and AGAP inhibited the peak currents of hNaV1.4 and hNaV1.5; however, W38G induced a much weaker inhibition of both channels than AGAP. Accordingly, W38G exhibited much less toxic effect on both skeletal and cardiac muscles than AGAP in vivo. The analgesic activity of W38G and AGAP were verified in vivo as well, and W38G retained analgesic activity similar to AGAP. Inhibition to both NaV1.7 and NaV1.8 was involved in the analgesic mechanism of AGAP and W38G. These findings indicated that Trp38 was a key amino acid involved in the biotoxicity of AGAP, and the AGAP mutant W38G might be a safer alternative for clinical application because it retains the analgesic efficacy with less toxicity to skeletal and cardiac muscles.


Download here

Back

Nanion コーポレートブログ

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.