Total Synthesis of (−)‐Doliculide,Structure–Activity Relationship Studies and Its Binding to F‐Actin |
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Authors: | Dr. Kiran Matcha Dr. Ashoka V. R. Madduri Dr. Sayantani Roy Dr. Slava Ziegler Prof. Dr. Herbert Waldmann Dr. Anna K. H. Hirsch Prof. Dr. Adriaan J. Minnaard |
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Affiliation: | 1. Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen (The Netherlands);2. Department of Chemical Biology, Max‐Planck Institute of Molecular Physiology, Otto‐Hahn Strasse 11, 44227 Dortmund (Germany) |
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Abstract: | Actin, an abundant protein in most eukaryotic cells, is one of the targets in cancer research. Recently, a great deal of attention has been paid to the synthesis and function of actin‐targeting compounds and their use as effective molecular probes in chemical biology. In this study, we have developed an efficient synthesis of (?)‐doliculide, a very potent actin binder with a higher cell‐membrane permeability than phalloidin. Actin polymerization assays with (?)‐doliculide and two analogues on HeLa and BSC‐1 cells, together with a prediction of their binding mode to F‐actin by unbiased computational docking, show that doliculide stabilizes F‐actin in a similar way to jasplakinolide and chondramide C. |
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Keywords: | actin anticancer agents asymmetric synthesis cyclodepsipeptides molecular modeling |
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