New leads for Anti-Cancer Drug Development

人们一直需要开发新的抗癌药物，特别是那些针对实体肿瘤的药物。在过去，植物一直是抗癌药物的极其宝贵的来源，包括世界上最畅销的抗癌药物S，从太平洋红豆杉中分离出来的紫杉醇。然而，这类分子通常很复杂，而且制造或从自然来源提取往往非常昂贵。到目前为止，从植物中提取的蛋白质分子作为潜在的抗癌药物还很少受到关注，因为制药公司一直专注于有机分子。原则上，以蛋白质为基础的分子可以生产得更便宜，从而比现有药物更广泛地供患者使用。所需要的只是具有足够抗癌活性的先导分子或蛋白质，作为进一步优化的基础。我们已经发现了一类名为环肽的植物蛋白，最近被证明有相当大的前景作为抗癌药物。在目前的项目中，我们将使用合成化学来修饰这一新的蛋白质家族表面的选定氨基酸，以确定分子的哪些部分负责它们的活动。我们将利用这些信息来设计改进的类似物。该项目是由昆士兰大学分子生物科学研究所的研究人员与瑞典乌普萨拉大学的研究人员和临床医生合作完成的，前者在所需的多肽化学方面拥有专业知识，后者拥有一系列测试和临床专业知识来测试新分子。这两个小组都主要参与了植物蛋白环肽家族的发现，并致力于将其开发为令人兴奋的新抗癌药物。

There is an ongoing need for the development of new anticancer drugs, particularly those directed against solid tumours. In the past plants have been an extremely valuable source of anticancer agents, including the world s best selling anticancer drug, Taxol, isolated from the Pacific Yew tree. However, such molecules are typically complex and often very expensive to manufacture or extract from natural sources. So far very little attention has been paid to protein-based molecules from plants as potential anticancer agents because pharmaceutical companies have focused on organic molecules. In principle protein-based molecules could be produced much more cheaply and thus made available more widely to patients than existing drugs. All that is required are the lead molecules, or proteins that display sufficient anticancer activity to be used as the basis for further optimization. We have discovered a family of plant proteins called the cyclotides that have recently been shown to have considerable promise as anticancer agents. In the current project we will use synthetic chemistry to modify selected amino acids on the surface of this new family of proteins to determine which parts of the molecules are responsible for their activity. We will use this information to design improved analogues. The project is a collaboration between researchers at the Institute for Molecular Bioscience, University of Queensland, who have expertise in the required peptide chemistry and researchers and clinicians at Uppsala University, Sweden who have a range of assays and clinical expertise to test the new molecules. Both groups have been centrally involved in the discovery of the cyclotide family of plant proteins and are committed to developing them as exciting new anticancer agents.