Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom; email:
Annu Rev Biochem. 2014;83:1-44. doi: 10.1146/annurev-biochem-041612-095236. Epub 2014 Jan 15.
My scientific journeys began at Oxford nearly 50 years ago. My paths have taken me from magnetic resonance through enzyme systems to antibodies, which led directly to glycobiology. Oxford University's first industrial grant helped the development of the technology for isolating and sequencing oligosaccharides from glycoproteins. This technology was disseminated through a spin-off company, Oxford GlycoSystems, and by the establishment of the Glycobiology Institute. The technology gave rise to the concept of glycoforms, which allow diversification of a protein's properties. Iminosugars, which are glucosidase inhibitors, can interfere with the initial steps of glycan processing on proteins and inhibit three-dimensional folding of glycoproteins. Glucosidase targets for therapy include viral envelope glycoproteins. Clinical trials of an iminosugar as an antiviral for dengue virus are under way. Another iminosugar activity, inhibition of glycolipid synthesis, resulted in a drug for Gaucher disease, which was approved worldwide in 2002. The success of the company and the institute allowed me to undertake several initiatives, in the United Kingdom and abroad, that might help the paths of future generations of scientists.
我的科研之旅始于近 50 年前的牛津。我的研究路径从磁共振技术到酶系统再到抗体，最终直接导向糖生物学。牛津大学的第一笔工业资助有助于开发从糖蛋白中分离和测序寡糖的技术。这项技术通过一家名为 Oxford GlycoSystems 的衍生公司以及糖生物学研究所得以传播。这项技术催生了糖型这一概念，使蛋白质的特性多样化。作为葡萄糖苷酶抑制剂的亚氨基糖可以干扰蛋白质上聚糖加工的初始步骤，并抑制糖蛋白的三维折叠。用于治疗的葡萄糖苷酶靶点包括病毒包膜糖蛋白。正在进行临床试验，用亚氨基糖作为登革热病毒的抗病毒药物。另一种亚氨基糖的活性，即抑制糖脂合成，导致了治疗戈谢病的药物的诞生，该药物于 2002 年在全球获得批准。公司和研究所的成功使我能够在英国和国外开展了几项举措，这些举措可能有助于未来几代科学家的发展。
