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药物与靶物质(酶、受体、核酸等)相互作用时的构象是药物设计所需探讨的重要环节,以往的研究方法所探索的药物分子多为固态或孤立状态,而药物发挥作用所经历的转运、代谢、起效的过程都是在生物液中进行的。利用核磁共振研究药物分子和靶物质在溶液中的构象,推测药物分子发挥作用所需的生物活性构象是80年代后发展起来的新技术,对药物-靶物质复合物进行NMR研究可获取新药设计所需的重要信息。本文介绍了新近发展起来研究大分子复合物的几种NMR方法,包括变位NOE,同位素编辑的质子NMR,氚代配基的2D NOE差异谱,全氚代受体,异核3D NMR以及4D核磁共振。同时讨论了这些方法的适用范围,并展望对药物设计将产生重大影响的NMR研究趋势。
The conformation of the interaction between the drug and the target substance (enzymes, receptors, nucleic acids, etc.) is an important part of the drug design. Most of the drug molecules explored in the past research methods are in a solid or isolated state, The transport, metabolism, the process of onset are carried out in the biological fluid. Using NMR to study conformations of drug molecules and target substances in solution, it is speculated that the biologically active conformation required for drug molecules to play a role is a new technology developed after the 1980s. A new drug design can be obtained by NMR study of drug-target substance complexes Important information needed. In this paper, several new NMR methods for the study of macromolecular complexes have been introduced, including displacement NOE, isotope-edited proton NMR, tritiated ligand 2D NOE difference spectra, all-tritiated receptor, heteronuclear 3D NMR and 4D Nuclear magnetic resonance. At the same time, the scope of application of these methods is discussed, and the trend of NMR research which will have a significant impact on drug design will be forecasted.