Chemical Modification of Alpha-Amanitin to Yield Derivatives Suitable for Conjugation to Proteins Via Reductive Alkylation

Cover Chemical Modification of Alpha-Amanitin to Yield Derivatives Suitable for Conjugation to Proteins Via Reductive Alkylation
Chemical Modification of Alpha-Amanitin to Yield Derivatives Suitable for Conjugation to Proteins Via Reductive Alkylation
Mullersman, Jerald Eric, 1956-
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In con- trast to OMAA-I, the CD spectra of all of the new derivatives were indistinguishable from that of OMA (Fig. II-3). Also, their color- reaction with cinn-HCl was violet compared with the rust color ob- tained with OMAA-I. As expected, only OMAA-NH- reacted with fluores- camine to yield a fluorescent product. FAB-MS of 0MA-C00H and 0MA-NH 2 revealed mass ions of the appropriate size for the proposed structures (Figs. II 1-3 and III-4).
Instability of the reductive amination products has b
...een detected after prolonged storage of frozen solutions. This destruction was associated with loss of the distinctive UV absorbances, e.g., at 304 nm (data not shown). Loss of the compounds was retarded when solutions were mildly acidic.
None of the new derivatives inhibited CT RNAP II as strongly as AMA. OMA-CN was the strongest inhibitor with a K. of 3 X 10" 9 M.
OMA-gly, OMA-pro, 0MA-C00H, and 0MA-NH 2 were much weaker inhibitors with Kys of 2.5 X 10" 7 M, 7 X 10" 6 M, 1 X 10" 7 M, and 1.7 X 10" 7 M, respectively.


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