Diphtheria toxin inactivates protein synthesis elongation factor 2 by attaching ADP-ribose to an unusual post-translational amino acid derivative, diphthamide, in the factor. Previously, we prepared ribosyl-diphthamide from the ADP-ribosyl-factor and proposed on the basis of NMR spectral analysis that it is 1-alpha-D-ribofuranosyl-2-[3-carboxyamido-3-(trimethylammonio++ +)propyl] histidine [N. J. Oppenheimer, and J.W. Bodley, (1981) J. Biol. Chem. 256, 8579-8581 and op. cit.]. Now, using fast atom bombardment mass spectrometry, the intact cation of ribosyl-diphthamide has been observed in the gas phase. The theoretical mass of the structure proposed for ribosyl-diphthamide uniquely agrees with the observed mass of the inact cation of the compound to within 2 ppm. Collisional activation decomposition mass spectral analysis provided additional structural confirmation. Thus, although the compound has not been synthesized, all available evidence appears uniquely consistent with the structure of ribosyl-diphthamide previously proposed.

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http://dx.doi.org/10.1016/0003-9861(84)90439-9DOI Listing

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