Hydrophobic collapse of taxol and taxotere solution conformations in mixtures of water and organic solvent
Hydrophobic collapse of taxol and taxotere solution conformations in mixtures of water and organic solvent
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DOI：
10.1021/ja00077a095
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发表时间：
1993-12
影响因子：
15
通讯作者：
D. Velde;Gunda Ingrid Georg;G. L. Grunewald;C. W. Gunn;L. Mitscher
中科院分区：
文献类型：
--
作者：
D. Velde;Gunda Ingrid Georg;G. L. Grunewald;C. W. Gunn;L. Mitscher
紫杉醇：R1= Ph，R2= Ac Taxotere：R= OBu '，R2= H微管和Taxol或Taxotere的结合态构象尚不清楚，基于已报道的Taxotere的晶体结构，已阐明了结合位点的潜在重要特征2。3 4567紫杉醇在氯仿4 -7和二氯甲烷8中的溶液构象似乎与晶体结构非常相似。在所有这些情况下，都有证据表明1 '酯羰基、2'羟基和3 'NH之间存在氢键网络，相对于相当刚性的紫杉烷环系统，该氢键网络构成了苯基异丝氨酸侧链。这种构象在固态和各种有机溶剂中的明显稳定性有助于紫杉醇侧链被“预组织”以这种构象结合微管的想法。9 '10最近发表了两项结合NMR和分子模拟研究的结果，表明在极性更强的溶液中（泰索帝的甲醇溶液，11紫杉醇的DMSO/水溶液12），
Taxol: R1= Ph, R2= Ac Taxotere: R= OBu’, R2= H microtubules and the bound-state conformation of Taxol or Taxotere are not known, potentially important features of the binding site have been suggested2 based on the reported crystal structure of Taxotere. 3 4567The solution conformation of Taxol, as it has been characterized in chloroform4-7 and methylene chloride, 8 seems to be very similar to that in the crystal structure. There is evidence inall these cases for a network of hydrogen bonding between the 1'ester carbonyl, the 2'hydroxyl, and the 3'NH which structures the phenylisoserine side chainrelative to the quite rigid taxane ring system. The apparent robustness of this conformation in the solid state and a variety of organic solvents has contributed to the idea that the Taxol side chain is “preor-ganized” to bind to microtubules in this conformation. 9’10 Very recently the results of two combined NMR and molecular modeling studies havebeen published which suggest that in more polar solutions (Taxotere in methanol, 11Taxol in DMSO/water12)