The structure of α-amanitin in dimethylsulfoxide solution

The backbone and side-chain conformations of the bicyclic octapeptide α-amanitin indimethylsulfoxide (DMSO) solution have ben deduced from analysis of the nmr spectrl parameters and conformational energy calculations. Several ambiguities in the nmr spectral assignments were resolved following a comparison with the recently published conformation of β-amanitin in the crystalline state. The peptide proton exchange and temperature coefficient data demonstrate strong intramolecular hyfrogen bonds for the GLY⁵ and Cys⁸ peptide protons. The vicinal proton coupling constants are consistent with the cyclic octapeptide udergoing chain reversl at the Ile⁶-Gly⁷ abd the Hyp²-Hyi³ dipeptide segments. The upfield shifts of the glycine and isoleucine protons demonstrate the folding of the indole ring of the Trp⁴-Cys⁸ brifge towards the Gly⁵-Ile⁶-Gly⁷ half of the Ile-amanitin molecule. The structure af α-amanitin in DMSO is defined by the (?ψ) backbone rotation angles Trp⁴(?90, ?60), Gly⁵ (+120, ?120), Ile⁶(?6, +120), Gly⁷ (+45, +60), Cys⁸(?120, ?60), Asn¹ (+175, ?175), Hyp² (?160, ?45), and Hyi³ (?90, ?60). The study demonstrates that the structure of α-amanitin in solution is similar to the structure f β-amanitin in the crystalline state.