The Effect of Truncation on SHK Toxin: Elimination of the Amino-Carboxyl Terminal (3-35) Disulfide Linkage Stabilizing the Amino and Carboxyl Terminal Segments

摘要

We have synthesized two truncated analogs ot ShK toxin which contain the main residues comprising the binding surface of the toxin. In both of these analogs, the disulfide bond which links the N and C terminal Cys residues has been eliminated. The remaining two disulfide bonds (Cys12-Cys28, Cys17-Cys32) have been retained in one analog and the other analog contains only the Cys17-Cys32 linkage. The CD spectrum of the bicyclic peptide appears to have a small amount of the helical structure whereas the monocyclic peptide spectrum appears to be idisordered. The activity of the bicyclic and monocyclic peptides were respectively reduced by 1360- and > 3000-fold relative to wild type ShK toxin.