Bioengineering of Cyclotides with Angiogenic Properties

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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.