THE ORIGIN OF THE SPECIFICITY IN THE RECOGNITION OF OLIGOSACCHARIDES BY PROTEINS
THE ORIGIN OF THE SPECIFICITY IN THE RECOGNITION OF OLIGOSACCHARIDES BY PROTEINS
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DOI：
10.1039/cs9891800347
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发表时间：
1989-09-01
影响因子：
46.2
通讯作者：
LEMIEUX, RU
中科院分区：
文献类型：
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作者：
LEMIEUX, RU
在细胞表面和生物体液中，碳水化合物结构的丰富镶嵌物以共价连接到脂质和蛋白质的复合寡糖的形式存在，在维持健康和疾病的建立中起关键作用。这些寡糖的长度通常小于20个糖残基。尽管如此，在结构、连接点、氧化或还原状态以及替代方面的可能变化提供了广泛的地形学，这些地形学作为一个极其庞大而复杂的词汇，有助于表达我们作为生活而体验到的精美诗歌。因此，正确定制寡糖是控制和指导健康细胞发育关键事件所需的智能来源。这些包括胚胎发生、受精、神经元发育、激素活动、细胞增殖及其组织成特定组织。细胞表面碳水化合物的显著变化随着肿瘤的进展而发生，这些变化似乎与可怕的转移状态密切相关。通常，用全细胞免疫获得的超过700种抗体针对寡糖结构。在对感染的免疫应答中识别细菌细胞壁多糖是宿主存活的主要贡献者。这些寡糖中的一些为细菌、病毒和病毒毒素的附着提供粘附位点。在过去的二十年里，这种对复杂寡糖结构对细胞生物学的普遍重要性的认识在很大程度上得到了发展，现在可能代表了分子生物学的主要前沿。因此，了解这些结构如何以及为什么被抗体、酶和凝集素的受体位点识别已成为主要关注的主题。本讲座将概述我的实验室对这个有趣的研究领域所做的贡献。我坚信我们已经取得了重要的进展，我们的发现对于触发生理反应的分子识别这一普遍课题具有重要意义。大约15年前，由于在化学合成所谓的人类血型抗原决定簇方面取得成功，我们开始积极参与这一领域。这种参与之所以出现，是因为人们已经知道，
The rich mosaic of carbohydrate structures which occur as complex oligosaccharides in covalent attachment to lipids and proteins both at cell surfaces and in biological fluids play key roles both in the maintenance of health and the establishment of disease. The length of these oligosaccharides is normally less than 20 sugar residues. Nevertheless, the possible changes in configuration, in points of attachment, in states of oxidation or reduction, and in substitution provide a wide range of topographies which serve as an extremely large and sophisticated vocabulary to assist in the expression of the exquisite poetry we experience as life. Thus, the correct tailoring of oligosaccharides serves as the source of the intelligence required for the control and guidance of key events for healthy cellular development. These include embryogenesis, fertilization, neuronal development, hormonal activities, cell proliferation, and their organization into specific tissues. Remarkable changes in the cell-surface carbohydrates occur with tumour progression and these changes appear to be intimately involved with the dreaded state of metastasis. Normally, more than 70 0 of the antibodies obtained on immunization with whole cells are directed against oligosaccharide structures. Recognition of bacterial cell-wall polysaccharides in immune response to infection is a major contributor to survival of the host. Some of these oligosaccharides provide adhesion sites for the attachment of bacteria, viruses, and viral toxins. This appreciation of the ubiquitous importance of complex oligosaccharide structures to cell biology has largely developed over the past two decades and now represents perhaps the major frontier of molecular biology. Consequently, an understanding of how and why these structures are recognized by the receptor sites of antibodies, enzymes, and lectins has become a subject of major concern. This lecture will outline contributions that my laboratory has made to this intriguing field for inquiry. I firmly believe that important progress was made and that our findings are of significance to the general subject of molecular recognition for the triggering of physiological responses. We became actively involved in this field about 15 years ago as the result of successes in the chemical synthesis of so-called human blood group antigenic determinants. This involvement arose because it had become known that the