CHEMICAL SYNTHESIS, STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF NOXIUSTOXIN, A POWERFUL BLOCKER OF LYMPHOCYTE VOLTAGE-DEPENDENT K+ CHANNELS

Two forms of the Centruduoides noxius scorpion noxiustoxin, containing an amidated and an acid C-terminus, were synthesized on a solid suppo rt by using Fmoc-chemistry and -(1H-benzotriazol-1-yl)-1,1,3,3-tetrame thyluronium hexafluorophosphate (HBTU) coupling. Comparison of the two synthetic forms with the native toxin by tryptic mapping and CD spect roscopy shows that noxiustoxin possesses an amidated C-terminus and th e same fold as all short scorpion toxins. Patch-clamp assays on B lymp hocytes demonstrate that noxiustoxin inhibits the voltage-dependent K channels with 2 nM affinity, but does not affect the Ca2+-activated K + channels. This toxin, because of its high affinity and specificity f or voltage-gated K+ channel, may provide a powerful tool in the invest igation of the role(s) of these channels in the T and B lymphocyte act ivation and proliferation. (C) 1995 Academic Press, Inc.