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Identification of ginkgolide targets in brain by photoaffinity labeling.


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 ?-tubulin isotypes. Selective photolabeling of ?-tubulin over ?-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 ?-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 ?-tubulin biology.

SUBMITTER: Kawamura A 

PROVIDER: S-EPMC5378617 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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Identification of ginkgolide targets in brain by photoaffinity labeling.

Kawamura Akira A   Washington Ilyas I   Mihai Doina M DM   Bartolini Francesca F   Gundersen Gregg G GG   Mark Milica Tesic MT   Nakanishi Koji K  

Chemical biology & drug design 20161110 4


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  ...[more]

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