Analysis and Exploitation of Oxygen-Dependent Modification to Ribosomes

核糖体是制造蛋白质的细胞内机器，但它们也包含蛋白质。最近BBSRC资助的工作导致发现核糖体蛋白质在蛋白质生物合成的重要位点上经历被称为羟基化的修饰，该修饰依赖于大气氧。最大的一类抗生素，如红霉素，靶向核糖体。核糖体的点突变赋予对这些抗生素的抗性。因此，应该有可能开发出选择性靶向未修饰核糖体而非修饰核糖体的化合物。肿瘤细胞通常是缺氧的，所以应该含有比正常细胞更好的羟基化的核糖体。我们建议使用后续资金来测试合成修饰的抗生素（由核糖体结构指导），以确定选择性抑制未修饰核糖体的化合物（反之亦然）。研究结果将用于支持专利申请，并在适当的情况下成立一家分拆公司。

Ribosomes are intracellular machines that make proteins, but they also contain proteins. Recent BBSRC funded work led to the discovery that ribosomal proteins undergo a modification, termed hydroxylation, dependent on atmospheric oxygen at sites of importance for protein biosynthesis. One of the largest classes of antibiotics, e.g. erythromycin, targets ribosomes. Point mutations to ribosomes confer resistance to such antibiotics. Hence it should be possible to develop compounds that selectively target unmodified over modified ribosomes. Tumour cells are often hypoxic so should contain ribosomes that are ales hydroxylated than normal cells. We propose to use Follow on Funding to test synthetically modified antibiotics (guided by ribosome structures) to identify compounds that selectively inhibit unmodified over modified (or vice versa) ribosomes. The results will be used to support patent applications and, if appropriate, to form a spin-out company.