McConville M J, Homans S W, Thomas-Oates J E, Dell A, Bacic A
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
J Biol Chem. 1990 May 5;265(13):7385-94.
Structures of the major glycolipids isolated from the protozoan parasite Leishmania major (strains V121 and LRC-L119), were elucidated by fast atom bombardment-mass spectrometry, two-dimensional proton NMR, methylation analysis, exoglycosidase digestions and mild acid hydrolysis. These glycolipids belong to a family of glycoinositolphospholipids (GIPLs), which contain 4-6 saccharide residues linked to alkylacylphosphatidylinositol (alkylacyl-PI) or lyso alkyl-PI. The general structure of the elucidated GIPLs can be expressed as follows: R-3Galf(alpha 1-3)Manp(alpha 1-3)Manp(alpha 1-4)GlcNp(alpha 1-6) alkylacyl-PI or lyso alkyl-PI where R = OH for GIPL-1; R = Galp(alpha 1- for GIPL-2; R = Galp(alpha 1-6)Galp (alpha 1- for GIPL-3 and R = Galp(alpha 1-3)Galf(alpha 1- for GIPL-A. The alkylacyl-PI lipid moieties are unusual in containing predominantly 18:0, 22:0, 24:0, or 26:0 alkyl chains and 12:0, 14:0, or 16:0 acyl chains. Remodeling of the lipid moieties may occur based on the finding that 1) lyso derivatives account for approximately 35% of the GIPL-3 fraction in strain V121 and 2) there is an increase in the proportion of 24:0 and 26:0 alkyl chains with elongation of the carbohydrate chain. Together with the elucidated structures, these properties are consistent with some of the GIPLs having a role as biosynthetic precursors to the major cell surface glycoconjugate, lipophosphoglycan. In particular, the saccharide sequences of GIPL-3, lyso-GIPL-3, and the glycan core of lipophosphoglycan (Turco, S. J., Orlandi, P. A., Homans, S. W., Ferguson, M. A. J., Dwek, R. A., and Rademacher, T. W. (1989) J. Biol. Chem. 264, 6711-6715) are identical. Finally, immunostaining of thin layer chromatograms with antibodies from patients with cutaneous leishmaniasis suggests that the major GIPLs are highly immunogenic and that the elevated anti-Gal antibodies, commonly seen in leishmaniasis patients, may be directed against terminal Galp(alpha 1-3)Galf residues.
通过快原子轰击质谱、二维质子核磁共振、甲基化分析、外切糖苷酶消化和温和酸水解，阐明了从原生动物寄生虫硕大利什曼原虫（菌株V121和LRC-L119）中分离出的主要糖脂的结构。这些糖脂属于糖基肌醇磷脂（GIPL）家族，其含有与烷基酰基磷脂酰肌醇（alkylacyl-PI）或溶血烷基-PI连接的4-6个糖残基。所阐明的GIPL的一般结构可表示如下：R-3Galf（α1-3）Manp（α1-3）Manp（α1-4）GlcNp（α-1-6）烷基酰基-PI或溶血烷基-PI，其中对于GIPL-1，R = OH；对于GIPL-2，R = Galp（α1- ；对于GIPL-3，R = Galp（α1-6）Galp（α1- ；对于GIPL-A，R = Galp（α1-3）Galf（α1- 。烷基酰基-PI脂质部分的不同寻常之处在于主要含有18:0、22:0、24:0或26:0的烷基链和12:0、14:0或16:0的酰基链。基于以下发现可能会发生脂质部分的重塑：1）溶血衍生物约占菌株V121中GIPL-3部分的35%；2）随着碳水化合物链的延长，24:0和26:0烷基链的比例增加。连同所阐明的结构，这些特性与一些GIPL作为主要细胞表面糖缀合物脂磷壁酸聚糖的生物合成前体的作用一致。特别是，GIPL-3、溶血-GIPL-3和脂磷壁酸聚糖的聚糖核心的糖序列（Turco，S. J.，Orlandi，P. A.，Homans，S. W.，Ferguson，M. A. J.，Dwek，R. A.，和Rademacher，T. W.（1989）J. Biol. Chem. 264，6711-6715）是相同的。最后，用皮肤利什曼病患者的抗体对薄层色谱图进行免疫染色表明，主要的GIPL具有高度免疫原性，并且在利什曼病患者中常见的抗Gal抗体升高可能是针对末端Galp（α1-3）Galf残基的。
