【摘要】 应用近代NMR波谱技术对孤啡肽OFQ及其片段OFQ_8-17的溶液结构进行了比较研究,测定了孤啡肽OFQ和片段OFQ_8-17在H₂O和TFE/H₂O两种溶剂条件下的2D-DQF-COSY,2D-TOCSY,2D-NOESY（ROESY）谱,完成了它们氨基酸残基的自旋系统识别和序列特异性归属,获得分子中质子化学位移的完全归属,根据NOE特征和主链偶合常数等结构参数确定了它们的特征二级结构,以NOE提供的距离约束,进行了距离几何,分子力学和分子动力学模拟,得到了孤啡肽OFQ在不同溶剂条件下的溶液结构.在H₂O溶剂中,孤啡肽OFQ在G3-F4-T5-G6处形成一复合型转角结构.在TFE/H₂O溶剂中,OFQ整个分子形成两亲性α-螺旋结构.而孤啡肽片段OFQ_8-17在这两种环境中均为伸展的无规结构.孤啡肽OFQ在类似膜环境（TFE/H₂O）下的α-螺旋结构可能为其活性构象.更多还原

【Abstract】 A comparative study on the solution conformation between OFQ and its fragment OFQ8-17 was carried out using 2D NMR experiments both in H2O and TFE/H2O. After completion of amino acid spin system recognition and the sequence-specific assignments, the regular secondary structure of OFQ and OFQ8-17 in different solvents were deduced from NOE patterns, and backbone coupling constants (3JHN-Ha). The solution structure of OFQ both in H2O and TFE/H2O was obtained using distance constraints derived from NOE cross peaks and dihedral angles constraints and was refined by DG, RMD and SA calculations. The structural feature of OFQ in water was characterized by a mixing type turn in segment of Gly3-Phe4-The5-Gly6 at 278 K. While the conformation of OFQ was identified as an amphipathic α-helix in TFE/H2O. However, OFQ8-17 demonstrated random conformation both in water and in TFE/ H2O. These results revealed that OFQ assumes amphipathic helical conformation in the membrane-like circumstances involved in the interaction with the receptor.更多还原