Shibata A, Morita K, Yamashita T, Kamaya H, Ueda I
Faculty of Pharmaceutical Sciences, Tokushima University, Japan.
J Pharm Sci. 1991 Nov;80(11):1037-41. doi: 10.1002/jps.2600801108.
Effects of volatile anesthetics (chloroform, halothane, and enflurane) on the secondary structure of poly(L-lysine) were analyzed by circular dichroism (CD). The relative proportions among alpha-helix, beta-sheet, and random-coil conformations were calculated by the curve-fitting method on the CD data. Volatile anesthetics partially transformed alpha-helix to beta-sheet but not to random-coil under the present experimental condition. When expressed by the anesthetic partial pressures in the gas phase in equilibrium with the solution, the values that partially transformed alpha to beta conformation by 10% were 1.1 x 10(-2), 4.7 x 10(-2), and 7.9 x 10(-2) atm for chloroform, halothane, and enflurane, respectively. The order of potency is in reasonable agreement with the order of the anesthetic potencies of the agents. The alpha-to-beta transition was completely reversible when anesthetics were purged by nitrogen gas. Volatile anesthetics disrupted the hydrogen bonds of alpha-helix backbones and rearranged them to form the beta-sheet conformation. The beta-sheet conformation is stabilized mainly by the hydrophobic interaction among methylene side groups of poly(L-lysine). Volatile anesthetics promoted the transition by enhancing the hydrophobic interaction among side-chains and by rearranging the hydrogen bonds in the peptide backbone.
采用圆二色光谱（CD）分析了挥发性麻醉剂（氯仿、氟烷和恩氟烷）对聚-L-赖氨酸二级结构的影响。通过对CD数据进行曲线拟合计算α-螺旋、β-折叠和无规卷曲构象之间的相对比例。在当前实验条件下，挥发性麻醉剂可使α-螺旋部分转变为β-折叠，但不会转变为无规卷曲。若以与溶液平衡的气相中麻醉剂的分压表示，使α-螺旋部分转变为β-构象达10%时的分压值，氯仿、氟烷和恩氟烷分别为1.1×10⁻²、4.7×10⁻²和7.9×10⁻² 大气压。其效能顺序与这些药剂的麻醉效能顺序合理一致。当用氮气吹扫麻醉剂时，α-到β-的转变是完全可逆的。挥发性麻醉剂破坏了α-螺旋主链的氢键，并使其重新排列形成β-折叠构象。β-折叠构象主要通过聚-L-赖氨酸亚甲基侧基之间的疏水相互作用得以稳定。挥发性麻醉剂通过增强侧链间的疏水相互作用以及重新排列肽主链中的氢键来促进这种转变。
