Bioengineering of Cyclotides with Angiogenic Properties

动脉粥样硬化，即动脉逐渐堵塞，是澳大利亚、欧洲、美国和日本的主要死亡原因。冠心病(CHD；冠状动脉阻塞)虽然在世界大部分地区继发于动脉粥样硬化，但仅在欧洲每年就造成近200万人死亡。在澳大利亚，冠心病是唯一的主要死亡原因。该项目旨在开发铅分子，用于开发能够刺激血管重建(即，打开堵塞的血管以改善血液流动)的血液循环缓慢或缓慢的组织的治疗方法。这种疗法将改善动脉粥样硬化和冠心病的治疗。多肽是一种小蛋白质，通常不够稳定，不能用作药物。在这个项目中，我们计划基于一种异常稳定的蛋白质家族来设计蛋白质分子，这种蛋白质家族被称为环肽。我们将通过化学方法合成环肽的类似物，这些环肽已经被改变，加入了不太稳定的小肽的活性，能够诱导治疗性血管生成。鉴于CHD的流行，有效疗法的开发可能会对该疾病的经济成本产生深远影响，在美国，每年的经济成本高达1332亿美元。这个项目涉及分子生物科学研究所的研究人员和血管生物学研究中心的研究人员之间的合作，前者在药物设计和蛋白质化学方面有专长，后者在血管生物学和血管工程方面有专长。这两个研究所都是昆士兰大学的一部分。

Atherosclerosis, a gradual clogging of the arteries, is the single leading cause of death in Australia, Europe, the USA and Japan. Coronary heart disease (CHD; clogging of the coronary arteries), while secondary to atherosclerosis in most of the world, accounts for nearly 2 million deaths per year in Europe alone. In Australia CHD is the single leading cause of death. This project is aimed at developing lead molecules for the development of therapeutics capable of stimulating revascularization (that is, opening up blocked vessels to improve blood flow) of tissues with slow or retarded circulation. Such therapeutics would improve the treatment of atherosclerosis and CHD. Peptides, small proteins, are generally not stable enough to be used as drugs. In this project we plan to engineer protein molecules based on an unusually stable family of proteins, known as the cyclotides. We will chemically synthesise analogues of cyclotides that have been altered to incorporate the activities of less stable small peptides that are able to induce therapeutic angiogenesis. Given the prevalence of CHD, the development of effective therapeutics could have a profound impact on the economic cost of the disease, which in the USA amounts to US$133.2 billion per year. This project involves collaboration between researchers from the Institute for Molecular Bioscience, who have expertise in drug design and protein chemistry, and researchers from the Centre for Research in Vascular Biology, who have expertise in vascular biology and vessel engineering. Both of these institutes are part of the University of Queensland.