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Structure analysis and immunopharmacological activities of mycolic acid-containing glycolipids in acid fast bacterial cell walls

抗酸细菌细胞壁中含分枝菌酸糖脂的结构分析及免疫药理学活性

基本信息

批准号：
60480162
负责人：
YANO Ikuya
金额：
$ 2.82万
依托单位：
Osaka City University (1986)Niigata University (1985)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

The most characteristic component of the cell walls of the acidfast bacteria, such as Mycobacteria and Nocardia, has been known to be "mycolic acid", a very high molecular weight 3-hydroxy fatty acid with a long alkyl chain at the 2-position. These acids are associated with cell wall skeleton via the esterification or with specific glycolipids. Since the cell wall components containing mycolic acids possess unique biological activities between the host and parasite relationships in the infection, such as immunoadjuvant activities, macrophage activating activities and antitumor activities, we have started to examine the structure-activity relationships of various mycolic acid-containing glycolipids in Nocardia, Rhodococcus and Gordona which are closely related taxonomically to Mycobacterium. The detailed structure of mycolic acid molecular species ranging from <C_(30)> to <C_(80)> from the glycolipids were demonstrated by using GC/MS and the granuloma forming activity of the glycolipids was shown to be affected deeply by the structure and acyl numbers of mycolic acids. Neutral glycolipids possessing glucose or trehalose as hydrophilic moiety and mycolic acids longer than <C_(40)> were shown to have a strong activity for the granuloma formation in mice. On the other hand, glycolipids possessing anionic charge or shorter chain mycolic acids did not show significant activity. These results show the both hydrophilic and hydrophobic structures of glycolipids play very important roles in immunopharmacological or biological response-modifiering activities.

已知耐酸细菌（例如分枝杆菌和诺卡氏菌）细胞壁的最具特征性的成分是“分枝菌酸”，一种在2位具有长烷基链的非常高分子量的3-羟基脂肪酸。这些酸通过酯化作用与细胞壁骨架结合或与特定的糖脂结合。由于含有分枝菌酸的细胞壁成分在感染中具有独特的宿主与寄生虫关系的生物活性，如免疫佐剂活性、巨噬细胞激活活性和抗肿瘤活性，因此我们开始研究与分枝杆菌分类密切相关的诺卡氏菌、红球菌和戈多纳菌中各种含分枝菌酸的糖脂的构效关系。使用GC/MS 证明了糖脂中从<C_(30)> 到<C_(80)> 的分枝菌酸分子种类的详细结构，并且糖脂的肉芽肿形成活性受到分枝菌酸的结构和酰基数的深刻影响。具有葡萄糖或海藻糖作为亲水部分和长于<C_(40)>的分枝酸的中性糖脂显示出对于小鼠肉芽肿形成具有强活性。另一方面，具有阴离子电荷或较短链分枝菌酸的糖脂没有表现出显着的活性。这些结果表明，糖脂的亲水性和疏水性结构在免疫药理学或生物反应调节活性中发挥着非常重要的作用。