合成嗜熱菌磷酸葡萄醣苷酯質及研究其酯多醣抗拮劑之可能

Abstract

先前的研究結果顯示，這四類嗜熱性菌株Meiothermus taiwanensis，Meiothermus ruber，Thermus thermophilus和Thermus oshimai，雖然是葛蘭氏陰性的細菌，但是卻不含有脂多醣（內毒素），反而含有比較多的磷酸醣酯和醣甘油酯。從Meiothermus taiwanensis和T. oshimai細胞膜中萃取分離得到的磷酸葡萄醣苷酯質混合物，發現此混合物在human THP-1 monocytes和blood-isolated primary monocytes可以正向調節白細胞介素-1b的量。此混合物含有兩種結構相似且不易分離的化合物，PGL1和PGL2，我們發現PGL2並不會促進前驅白細胞介素的產生反而會抑制PGL調節前驅白細胞介素的量，這顯示出在磷酸葡糖糖甘酯質混合物中PGL1是在細胞中促進白細胞介素產生的主要誘導物。除此之外，PGL的脂肪酸成分是由C15和C17組成，具有調節免疫活性的兩株菌 (M. taiwanensis and T. oshimai) C15的比例都較高，而無活性的另兩株菌 (T. thermophilus and M. ruber) C17的比例較高，這表示脂肪酸碳鍊長短可能會影響其免疫活性。 我們還發現磷酸葡萄糖苷酯質可以降低脂多醣的活性，換句話說，此化合物可能可以作為脂多醣拮抗劑的候選者。基於以上這些發現，我們的目標就是以有機合成的方式得到純的PGL1來解決脂肪酸碳鍊對活性的影響、找出PGL1的受體以及內毒素耐受性活性。這篇專題論文把重點放在PGL1不同脂肪酸碳鍊的全合成和內毒素耐受性的測試。

The structure of phosphoglycolipid have been well studied, but the real biological function of these compound are not cleared identified. According to our previous report, PGL1/PGL2 mixture from M. taiwanensis and T. oshimai, but not T. thermophilus and M. ruber, up-regulate interleukin-1b (IL-1b) production in human THP-1 monocytes and blood-isolated primary monocytes. In addition, PGL2 did not induce proIL-1 production but inhibited PGL1-mediated proIL-1 production, showing that PGL1 is the main inducer of proIL-1 production in PGL1/PGL2 mixture. Our lab found that PGL1 could decrease LPS activity (unpublished), in other words, PGL1 may have the possibility to become the candidate of LPS antagonist or else. For these reason, our target is to acquire the pure PGL1 by organic synthesis, to straighten out these questions, including the influence of the acyl chain of PGL1, receptor of PGL1, and the exdotoxin tolerance activity. This study is focused on the total synthesis of PGL1 in different length of alkyl chain, and the LPS tolerance activity in human THP-1 cell.