Vibrational Circular Dichroism Analysis Reveals a Conformational Change of the Baccatin III Ring of Paclitaxel: Visualization of Conformations Using a New Code for Structure-Activity Relationships
详细信息 查看全文
- 作者：Hiroshi Izumi ; Atsushi Ogata ; Laurence A. Nafie ; Rina K. Dukor
- 刊名：Journal of Organic Chemistry
- 出版年：2008
- 出版时间：March 21, 2008
- 年：2008
- 卷：73
- 期：6
- 页码：2367 - 2372
- 全文大小：321K
- 年卷期：v.73,no.6(March 21, 2008)
- ISSN：1520-6904
文摘
The comparison between measured and conformer-weighted calculated VCD spectra of the baccatin IIIring of paclitaxel and visualization of the conformations using the new code for structure-activityrelationships are reported for the first time. The VCD spectrum of paclitaxel closely resembles that ofthe baccatin III ring. The large characteristic 
CO VCD bands with bisignate signs (1732 cm-1, 
=-1.6 × 10-1; 1715 cm-1, = 2.4 × 10-1) strongly reflect the structural property of the family ofconformations bacc-ABC32F defined using the new code. The comparison with the conformation of thebaccatin III core in the electron micrograph of the crystal structure of tubulin-paclitaxel (1JFF) suggestsa conformational change of paclitaxel corresponding to a switch through the binding with 
-tublin andthe intermolecular interactions involving the hydroxyl group (D) and carbonyl of acetoxy group (E). Therepresentation of conformational codes allows complicated conformations to be very easily comparedand facilitates future computational analyses such as those for the large-molecule calculations as well asgenome analysis.
CO VCD bands with bisignate signs (1732 cm-1, =-1.6 × 10-1; 1715 cm-1, = 2.4 × 10-1) strongly reflect the structural property of the family ofconformations bacc-ABC32F defined using the new code. The comparison with the conformation of thebaccatin III core in the electron micrograph of the crystal structure of tubulin-paclitaxel (1JFF) suggestsa conformational change of paclitaxel corresponding to a switch through the binding with -tublin andthe intermolecular interactions involving the hydroxyl group (D) and carbonyl of acetoxy group (E). Therepresentation of conformational codes allows complicated conformations to be very easily comparedand facilitates future computational analyses such as those for the large-molecule calculations as well asgenome analysis.