Identification of ginkgolide targets in brain by photoaffinity-labeling.
Chem Biol Drug Des. 2016 Oct 15. Epub 2016 Aug 15. PMID: 27743504
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 ofα-tubulin isotypes. Selective photolabeling of α-tubulin over β-tubulin, which is equally abundant in brain, suggested that ginkgolides might modulate microtubule (MT) biology differently than typical MT-binding agents, such as taxol. In fact, ginkgolide A did not affect MT polymerization or cellproliferation; instead, it inhibited detyrosination of α-tubulin and reorientation of microtubule-organizing centers (MTOCs). Taken together, the current findings indicate that ginkgolides constitute a new class of MT-binding agents with distinct effects on α-tubulin biology. This article is protected by copyright. All rights reserved.