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探测生物结构的方法Chemical probes beat antibodies at own game
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Chemical probes beat antibodies at own game An interpretation of the binding of the synthetic proteins to proteins inside blood vessels. Credit: Karl Harrison. A new way of detecting biological structures could help in the fightagainst disease. The new method, developed by scientists at OxfordUniversity, uses chemistry to assemble proteins into ‘protein probes’that can be sent into the body to, for instance, detect inflammationand disease in the brain. The human body’s immune system uses its own‘protein probes’ – antibodies – to seek out foreign objects such asbacteria and viruses. These antibodies are proteins shaped to ‘fit’around parts of a target structure rather like a hand gripping a doorhandle. Scientists managed to replicate this process for the first timein 1975 with the creation of monoclonal antibodies now widely used invaccines and biotechnology. ‘We think of antibodies as natural but the ones we use fordetection are not always that great at binding to certain structuresand in some ways the binding of antibodies to their targets is prettyunrepresentative of other protein-to-protein interactions,’ saidProfessor Ben Davis of Oxford’s Department of Chemistry who led thework, ‘our protein probes, created using chemical rather thanbiological techniques, are sometimes better at binding with targetsthan antibodies because they can mimic natural protein partners moreclosely.’ By attaching themselves to binding proteins on target cells,such as chronically inflamed brain cells, the probes stain the tissueand this staining can then be detected with a microscope or othermethods. A report on the research, entitled ‘Expandingthe diversity of chemical protein modification allowspost-translational mimicry’, has just been published in the journal Nature. It details how Oxford scientists used chemistry to control themodification of proteins from simple chains of amino acids to complexstructures similar to those seen in nature. By combining thesestructures with ready-made protein scaffolds the research team werethen able to produce and test protein probes designed to targetspecific biological structures. In some cases they found that theirprotein probes were better at binding with some protein partners thanmonoclonal antibodies. ‘The strategy behind these probes could be useful for makingsynthetic proteins in many areas of medicine and science’ saidProfessor Davis ‘but the real goal behind making these modified proteinstructures using chemistry is that we hope it could enable us to findclues as to how we have ended up with such complex life forms fromsurprisingly few genes.’ 一种新的探测生物结构的方法或许将帮助治疗很多疾病，这一由牛津大学科学家们发明的方法，利用了化学手段将蛋白质聚集成“蛋白探针”，它们能被送入人体来检测多种疾病及炎症。结果发表在最新的《Nature》上。人体的免疫系统有自己的“蛋白探针”——抗体，抗体可以识别外来病原例如细菌和病毒，这些抗体有独特的形状以和目标的结构匹配，来形成“钥匙-锁”模型。早在1975年，科学家就试图用单克隆抗体来模拟这一过程，单克隆抗体目前广泛用于疫苗和生物技术领域。 牛津化学系的BenDavis教授是项目负责人，他说：“天然抗体效果不总是那么好的，而我们的新型蛋白探针利用的是化学技术得到，因此能更精确的模拟天然蛋白结构，从而结合的效果更佳。”通过和目标细胞的蛋白质结合，例如慢性脑炎细胞，这些探针就会在组织中留下记号，而这些记号又可以通过显微镜或其它方法探测到。 文章中详细介绍了科学家是如何控制简单的氨基酸链模拟自然界的复杂结构的。将这一技术和已有的蛋白质模板结合就可以制造和测试针对特定生物结构的蛋白探针。在某些情况下，科学家发现这些蛋白探针和目标蛋白质结合的效果要比单克隆抗体更好。 Davis最后表示：“这些探针背后的技术对于研制医药等领域的合成蛋白是非常有帮助的。” 觉得好就给以回复！ [ Last edited by 小红豆 on 2007-5-20 at 13:46 ] |
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