Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis
Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis
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DOI：
10.1126/science.276.5315.1125
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发表时间：
1997-05-16
期刊：
影响因子：
56.9
通讯作者：
Bertozzi, CR
中科院分区：
文献类型：
--
作者：
Mahal, LK;Yarema, KJ;Bertozzi, CR
细胞表面寡糖可以被设计为显示不寻常的官能团，用于细胞表面的选择性化学重塑。 N-乙酰甘露糖胺的非天然衍生物具有酮基，被转化为相应的唾液酸并通过代谢结合到细胞表面寡糖中，导致细胞表面显示酮基。然后，细胞表面上的酮基可以在生理条件下与带有互补反应性官能团（例如酰肼）的分子共价连接。这种类型的细胞表面反应应该被证明有助于将新的识别表位（例如肽、寡糖或小有机分子）引入到细胞表面上，以及随后调节细胞-细胞或细胞-小分子结合事件。选择性药物输送的例子证明了该技术的多功能性。通过与酮基选择性缀合，用生物素修饰细胞，并在蓖麻毒蛋白 A 链-亲和素缀合物存在的情况下选择性杀死细胞。
Cell surface oligosaccharides can be engineered to display unusual functional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of N-acetylmannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell-small molecule binding events. The versatility of this technology was demonstrated by an example of selective drug delivery. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate.