Abstract
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 GLY^5^ and Cys^8^ peptide protons. The vicinal proton coupling constants are consistent with the cyclic octapeptide udergoing chain reversl at the Ile^6^‐Gly^7^ abd the Hyp^2^‐Hyi^3^ dipeptide segments. The upfield shifts of the glycine and isoleucine protons demonstrate the folding of the indole ring of the Trp^4^‐Cys^8^ brifge towards the Gly^5^‐Ile^6^‐Gly^7^ half of the Ile‐amanitin molecule. The structure af α‐amanitin in DMSO is defined by the (ϕψ) backbone rotation angles Trp^4^(−90, −60), Gly^5^ (+120, −120), Ile^6^(−6, +120), Gly^7^ (+45, +60), Cys^8^(−120, −60), Asn^1^ (+175, −175), Hyp^2^ (−160, −45), and Hyi^3^ (−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.