Two myo-inositol derivatives having an N^α,N^ε-diacetyl-L-lysine (Ac₂Lys) moiety linked to the inositol 1-O-position through a self-cleavable linker and a metabolically stable 2-azidoethyl group linked to the inositol 3-O- and 4-O-positions, respectively, were designed and synthesized. The Ac₂Lys moiety blocking the inositol 1-O-position required for GPI biosynthesis was expected to be removable by a combination of two enzymes, histone deacetylase (HDAC) and cathepsin L (CTSL), abundantly expressed in cancer cells, but not in normal cells, to transform these inositol derivatives into biosynthetically useful products with a free 1-O-position. As a result, it was found that these inositol derivatives could be incorporated into the glycosylphosphatidylinositol (GPI) biosynthetic pathway by cancer cells, but not by normal cells, to express azide-labeled GPIs and GPI-anchored proteins on cell surfaces. Consequently, this study has established a novel strategy and new molecular tools for selective metabolic labeling of cancer cells, which should be useful for various biological studies and applications.

中文翻译：

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Nα，Nε-二乙酰基-1-赖氨酸-肌醇偶联物的合成和评估，作为GPI和GPI固定蛋白代谢工程的癌症选择性探针。

两个肌醇具有肌醇衍生物Ñ ^α，Ñ ^ε -diacetyl-大号赖氨酸（AC ₂的Lys）部分连接于肌醇1- Ô位上通过自切割的接头并连接到一个代谢稳定的2-叠氮基乙基组分别设计和合成了肌醇的3- O-和4- O-位。Ac ₂ Lys部分阻断肌醇1- O预期可以通过在癌细胞中大量表达但在正常细胞中不大量表达的两种酶（组蛋白脱乙酰基酶（HDAC）和组织蛋白酶L（CTSL））的组合来去除GPI生物合成所需的位置，以将这些肌醇衍生物转化为生物合成有用的化合物产品带有1- O-自由位置。结果，发现这些肌醇衍生物可以通过癌细胞而不是正常细胞掺入糖基磷脂酰肌醇（GPI）生物合成途径中，以在细胞表面表达叠氮化物标记的GPI和GPI锚定的蛋白质。因此，这项研究为癌细胞的选择性代谢标记建立了一种新的策略和新的分子工具，这对于各种生物学研究和应用应该是有用的。