Synthetic glycosylphosphatidylinositol (GPI) anchors: how these complex molecules have been made.
Synthetic glycosylphosphatidylinositol (GPI) anchors: how these complex molecules have been made.
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DOI：
10.1039/c0np00064g
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发表时间：
2011-05
影响因子：
11.9
通讯作者：
Al-Maharik N
中科院分区：
文献类型：
--
作者：
Nikolaev AV;Al-Maharik N
糖基磷脂酰肌醇（gpi）是一类天然的糖基磷脂，可将蛋白、糖蛋白和脂磷酸聚糖固定在真核细胞的膜上。GPI锚点广泛存在于寄生原生动物中，其中GPI锚定的粘蛋白和磷酸聚糖丰富，并在寄生虫表面形成致密的保护层（糖萼）。这种类型的锚似乎在这些生物中比在高等真核生物中出现的频率要高得多。自从1988年第一个完整的GPI结构分配以来，超过50个糖基磷脂酰肌醇已经被结构表征。GPI锚点的功能（除了将上述生物聚合物连接到膜上的明确功能外）已被广泛讨论。gpi和gpi锚定聚合物的高横向迁移率似乎积极促进分子从细胞表面的选择性释放和细胞间膜蛋白的交换。还有证据表明，GPIs和/或其代谢物可以作为次级信使，调节包括胰岛素产生、胰岛素介导的信号转导、细胞增殖和细胞-细胞识别在内的生物事件。它们作为调节过程的介质的发现使得这些化合物及其类似物的化学制备引起了极大的兴趣。本文综述了近二十年来在原生动物寄生虫、酵母和哺乳动物中GPI锚点和相关糖缀合结构的化学合成方面的进展。本文还讨论了结核分枝杆菌结构相关的原核糖缀合物的合成。
Glycosylphosphatidylinositols (GPIs) are a class of natural glycosylphospholipids that anchor proteins, glycoproteins and lipophosphoglycans to the membrane of eukaryotic cells. GPI anchors are widely present in parasitic protozoa, where GPI-anchored mucins and phosphoglycans are abundant and form a dense protective layer (glycocalyx) on the surface of the parasites. This type of anchor appears to be present in these organisms with a much higher frequency than in higher eukaryotes. Since the first full assignment of a GPI structure in 1988, more than 50 glycosylphosphatidylinositols have been structurally characterised. The functions of GPI anchors (in addition to the clear one of linking the above biopolymers to membranes) have been extensively discussed. The high lateral mobility of GPIs and GPI-anchored polymers seems to actively facilitate the selective release of molecules from the cell surface and the exchange of membrane proteins between cells. There is also evidence that GPIs and/or their metabolites can act as secondary messengers, modulating biological events including insulin production, insulin-mediated signal transduction, cellular proliferation and cell–cell recognition. Their discovered role as mediators of regulatory processes makes the chemical preparation of these compounds and their analogues of great interest. This comprehensive review highlights the progress in the chemical synthesis of GPI anchors and related glycoconjugate structures from protozoan parasites, yeast and mammals in the last two decades. The synthesis of a structurally related prokaryotic glycoconjugate of Mycobacterium tuberculosis is also discussed.