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Figure 8 Structures of dolastatins and analogs.

as in epoxypironetin 23, was found to result in a substantially weaker antimitotic potency.68'69 It has been shown by systematic alanine scanning that pironetin binds covalently at Lys352 of alpha-tubulin. This lysine residue is positioned near the opening of a small pocket in alpha-tubulin facing the beta-tubulin of the next dimer, perhaps destabilizing the protein-protein interaction.70

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