Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
Eur Biophys J. 2011 Apr;40(4):359-70. doi: 10.1007/s00249-011-0672-9. Epub 2011 Feb 3.
Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for determining the structures, dynamics and interactions of molecules, and the derived information can be useful in drug design applications. This article gives a brief overview of the role of NMR in drug design and illustrates this role with examples studied in our laboratory in recent years on disulfide-rich peptides, including cyclotides and conotoxins. Cyclotides are head-to-tail cyclized proteins from plants that are exceptionally stable and hence make useful templates for the stabilization of bioactive peptide epitopes as well as potential leads for anti-HIV drugs. Natural cyclotides target cell membranes, so understanding cyclotide-membrane interactions is useful in applying cyclotides in drug design applications. NMR studies of these interactions are described in this article. Conotoxins are disulfide-rich peptides, from the venoms of marine cone snails, which are of pharmaceutical interest because they potently interact with a range of ion channels, transporters and other receptor sites implicated in disease states. Chemically re-engineering conotoxins to give them a cyclic backbone has been used to engender them with improved biopharmaceutical properties, such as are observed in cyclotides.
核磁共振波谱学（NMR）是一种用于确定分子结构、动态和相互作用的强大技术，其衍生信息在药物设计应用中可能很有用。本文简要概述了 NMR 在药物设计中的作用，并通过近年来我们实验室在富含二硫键的肽（包括环肽和 conotoxin）研究方面的例子来说明这一作用。环肽是来自植物的头尾环化蛋白，异常稳定，因此可用作稳定生物活性肽表位的模板以及抗 HIV 药物的潜在先导物。天然环肽以细胞膜为靶标，因此了解环肽-膜相互作用对于将环肽应用于药物设计应用中是有用的。本文描述了这些相互作用的 NMR 研究。conotoxin 是富含二硫键的肽，来自海洋圆锥蜗牛的毒液，具有药物应用价值，因为它们能够与多种离子通道、转运体和其他与疾病状态相关的受体位点强烈相互作用。对 conotoxin 进行化学重工程改造，使其具有环状骨架，已被用于改善其生物制药特性，如在环肽中观察到的特性。
