Chemical Synthesis, Structural and Functional Characterization of Noxiustoxin, a Powerful Blocker of Lymphocyte Voltage-Dependent K+ Channels

E. Drakopoulou, J. Cotton, H. Virelizier, E. Bernardi, A.R. Schoofs, M. Partiseti, D. Choquet, G. Gurrola, L.D. Possani, C. Vita
Biochemical and Biophysical Research Communications. 1995-08-01; 213(3): 901-907
DOI: 10.1006/bbrc.1995.2214

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1. Biochem Biophys Res Commun. 1995 Aug 24;213(3):901-7.

Chemical synthesis, structural and functional characterisation of noxiustoxin, a
powerful blocker of lymphocyte voltage-dependent K+ channels.

Drakopoulou E(1), Cotton J, Virelizier H, Bernardi E, Schoofs AR, Partiseti M,
Choquet D, Gurrola G, Possani LD, Vita C.

Author information:
(1)CEA Département d’Ingénierie et d’Etudes des Protéines, CE Saclay,
Gif-sur-Yvette, France.

Two forms of the Centrudoides noxius scorpion noxiustoxin, containing an amidated
and an acid C-terminus, were synthesized on a solid support by using
Fmoc-chemistry and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium
hexafluorophosphate (HBTU) coupling. Comparison of the two synthetic forms with
the native toxin by tryptic mapping and CD spectroscopy shows that noxiustoxin
possesses an amidated C-terminus and the same fold as all short scorpion toxins.
Patch-clamp assays on B lymphocytes demonstrate that noxiustoxin inhibits the
voltage-dependent K+ channels with 2 nM affinity, but does not affect the
Ca(2+)-activated K+ channels. This toxin, because of its high affinity and
specificity for voltage-gated K+ channel, may provide a powerful tool in the
investigation of the role(s) of these channels in the T and B lymphocyte
activation and proliferation.

DOI: 10.1006/bbrc.1995.2214
PMID: 7654252 [Indexed for MEDLINE]

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