Identification of ginkgolide targets in brain by photoaffinity labeling |
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| Authors: | Akira Kawamura Ilyas Washington Doina M. Mihai Francesca Bartolini Gregg G. Gundersen Milica Tesic Mark Koji Nakanishi |
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| Affiliation: | 1. Department of Chemistry, Hunter College, New York, NY, USA;2. Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY, USA;3. Department of Ophthalmology, Columbia University Medical Center, New York, NY, USA;4. Department of Pathology and Cell Biology, Columbia University, New York, NY, USA;5. Proteomics Resource Center, The Rockefeller University, New York, NY, USA;6. Department of Chemistry, Columbia University, New York, NY, USA |
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| Abstract: | Ginkgolides are terpene trilactones in Ginkgo biloba, a popular medicinal herb for memory disorders. Although ginkgolides are known for various neurobiological effects, their macromolecular target in brain is unknown. In this work, we employed benzophenone derivatives of ginkgolides to identify their binding target in brain. Photolabeling of bovine hippocampus homogenates identified a series of α‐tubulin isotypes. Selective photolabeling of α‐tubulin over β‐tubulin, which is equally abundant in brain, suggested that ginkgolides might modulate microtubule biology differently than typical microtubule‐binding agents, such as taxol. In fact, ginkgolide A did not affect microtubule polymerization or cell proliferation; instead, it inhibited detyrosination of α‐tubulin and reorientation of microtubule‐organizing centers. Taken together, the current findings indicate that ginkgolides constitute a new class of microtubule‐binding agents with distinct effects on α‐tubulin biology. |
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| Keywords: | benzophenone detyrosination
Ginkgo biloba
mass spectrometry α ‐tubulin |
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