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

分枝杆菌和诺卡氏菌等抗酸细菌细胞壁的最具特征的成分一直被认为是“分枝杆菌酸”，这是一种在2-位带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或与特定的糖脂结合。由于含有霉菌酸的细胞壁成分在宿主和寄生虫感染关系中具有独特的生物活性，如免疫佐剂活性、巨噬细胞激活活性和抗肿瘤活性，我们已经开始研究诺卡氏菌、红球菌和戈多纳等在分类学上与分枝杆菌密切相关的各种含有真菌酸的糖脂的构效关系。用GC/MS分析了糖脂中~lt；C_(30)&gt；到~lt；C_(80)&gt；的详细结构，发现糖脂的肉芽肿形成活性受菌酸的结构和酰基数的影响很大。含有葡萄糖或海藻糖的中性糖脂和长于~lt；C_(40)&gt；的真菌酸对小鼠肉芽肿的形成有很强的活性。另一方面，具有阴离子电荷或短链霉菌酸的糖脂没有显示出显著的活性。这些结果表明，糖脂的亲水和疏水结构在免疫药理或生物反应修饰活性中起着非常重要的作用。

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.