GAL GLYCOCONJUGATES

这个项目的目的是研究糖偶联物与 在哺乳动物中，Galα1导致3Gal表位。这些化合物 特别令人感兴趣，因为它们独特的进化 分发。它们普遍存在于非灵长类动物的某些组织中 哺乳动物和新大陆的猴子。相比之下，人类、猿类和 东半球的猴子只有在一种神秘的、残留的 形式。此外，东半球的猴子、猿类和人类生产 通常是大量的自然产生的抗体(抗半乳糖) 到这座建筑。对人类的初步研究表明， 抗Gal和Galα1相互作用导致3Gal 新发现的表位，介导正常基因的移除 衰老的红细胞，在某些情况下，可能 促进病理性红细胞加速清除。最近 我们制备了一种小鼠单抗(Gal-13)，它可以 具有与抗Gal相同的结合特异性，识别 独有的半乳糖α1导致3半乳糖共轭化合物。这 单抗将成为研究的有用工具。 在本申请中描述的。 将使用三种方法来研究其分布、结构 并在哺乳动物体内生物合成这些糖结合物。1) 分类学和组织化学分析将由 抗Gal和Gal-13在几种组织上的免疫染色 从各种哺乳动物中获得的细胞系。平行染色 将使用凝集素Bandeiraea Simicifolia进行研究 I-B4，它似乎表现出类似的特异性，但不是 完全一样，和反Gal一样。2)GalAlpha的结构分析 糖脂和3-半乳糖基糖偶联物 小鼠红细胞、脑和肾组织中糖蛋白的分离 精选的哺乳动物。3)半乳糖α1的生物合成分析 通过研究组织将导致3Gal糖偶联物的产生 α1的分布导致3半乳糖基转移酶， 该酶的纯化及其底物性质的研究 专一性。这些研究将提供全面的信息 半乳糖α1导联的进化和生化特征 到哺乳动物中的3-半乳糖偶联物。关于Gal的后续研究 Alpha 1导致人体组织中的3Gal糖偶联物 根据在这个项目中获得的信息。

The purpose of this project is to study glycoconjugates with the Gal alpha 1 leads to 3Gal epitope in mammals. These compounds are of special interest because of their unique evolutionary distribution. They are prevalent in some tissues of non-primate mammals and New World monkeys. In contrast, man, apes and Old World monkeys have this epitope only in a cryptic, vestigial form. Moreover, Old World monkeys, apes and man produce usually large amounts of a naturally occurring antibody (anti-Gal) to this structure. Preliminary studies in man have shown that the interaction between anti-Gal and Gal alpha 1 leads to 3Gal epitopes exposed de novo, mediates the removal of normal senescent red cells and, under certain circumstances, may promote accelerated removal of pathologic red cells. Recently we have produced a mouse monoclonal antibody (Gal-13) which has the same binding specificity as anti-Gal, recognizing exclusively Gal alpha 1 leads to 3Gal glycoconjugates. This monoclonal antibody will be a useful tool for the research described in this application. Three approaches will be used to study the distribution, structure and biosynthesis of these glycoconjugates in mammals. 1) Taxonomical and histochemical analyses will be done by immunostaining with anti-Gal and Gal-13 on several tissues and cell lines obtained from various mammals. Parallel staining studies will be performed with the lectin, Bandeiraea simplicifolia I-B4, which seems to display a specificity similar, but not identical, to that of anti-Gal. 2) Structural analyses of Gal alpha 1 leads to 3Gal glycoconjugates will be done on glycolipids and glycoproteins isolated from red cells, brain and kidney tissue of selected mammals. 3) Analysis of the biosynthesis of Gal alpha 1 leads to 3Gal glycoconjugates will be done by studying the tissue distribution of alpha 1 leads to 3 galactosyl-transferase, purification of this enzyme and characterization of its substrate specificity. These studies will provide comprehensive information on the evolutionary and biochemical aspects of Gal alpha 1 leads to 3Gal glycoconjugates in mammals. Subsequent studies on Gal alpha 1 leads to 3Gal glycoconjugates in human tissues will be based on the information obtained in this project.