MVIIA and MVIIB ω‐conotoxins were chosen to investigate the effect of experimental conditions on their conformations, because of the presence of three disulfide bridges in these toxins. There were no significant effects of ion‐source temperature, cone voltage, pH and percentage of cosolvent. We show that charge state distributions (CSDs) observed in their electrospray mass spectra are not a true reflection of the behaviour in the bulk solution because of electrostatic effects during the ion‐evaporation process in the ion source. As a result it is not possible to deduce from the observed CSDs that some basic amino acids are hidden in the core of the peptide structure. This is important in view of the complementary finding that nearly all labile hydrogens are rapidly exchanged in deuterated solvents. The mass spectrometry results can be reconciled with results of NMR experiments and molecular calculations from the literature. Copyright © 2000 John Wiley & Sons, Ltd.

To examine the conformation of α-dendrotoxin, charge state distributions (CSD)and hydrogen/deuterium (H/D)isotopic exchange using electrospray-ionization mass spectrometry [ES-MS] have been used. Here, it cannot be deduced from the CSDs that some basic residues are hidden in the core of the structure. At neutral pH, the CSDs reflect the equilibrium bulk solution exactly. Seven basic residues seem to be shielded from the solvent, according to calculations from the X-ray structure. But, under acidic conditions, the CSDs observed in mass spectra are not a true reflection of the equilibrium bulk solution, partly because of an increased intramolecular electrostatic effect with the gaseous ions. H/D exchange experiments show that three to seven hydrogens are involved in hydrogen bonds. The resistance to urea denaturation has also been investigated. Urea and 1,4-dithiothreitol (DTT)denaturation together lead to unfolded conformers. During this reduction of the bridges, it is observed that the Cys16–Cys40 and Cys32–Cys53 linkages are more accessible to the reducing agent than the Cys7–Cys57 linkage, which is very important by maintaining a compact fold.

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