Analysis and Exploitation of Oxygen-Dependent Modification to Ribosomes

核糖体是制造蛋白质的细胞内机器，但它们也含有蛋白质。最近，BBSRC资助的研究发现，核糖体蛋白在蛋白质生物合成的重要位点上发生了一种称为羟基化的修饰，这种修饰依赖于大气中的氧气。最大种类的抗生素之一，例如红霉素，是针对核糖体的。核糖体的点突变赋予了对这类抗生素的抗性。因此，应该有可能开发出选择性靶向未修饰核糖体的化合物。肿瘤细胞通常是缺氧的，因此应含有比正常细胞羟基化程度低的核糖体。我们建议使用后续资金来测试合成修饰的抗生素（以核糖体结构为指导），以确定选择性抑制未修饰的过修饰（反之亦然）核糖体的化合物。研究结果将用于支持专利申请，如果合适的话，还将成立一家衍生公司。

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.