while an unsaturated phospholipid DOPE known as a non-raft molecule was colocalized for approximately 40 ms. The lifetime of NeuAcLc4Cer was similar to those of GM3 and GM1, which represent raft-associated gangliosides, implying that lacto-series gangliosides might be involved in the lipid raft assembly.3.2 Extension of bicyclic glycosyl donor to α-glycosidation of KdoOwing to its structural similarity to sialic acid, the stereocontrol of Kdo glycosidation remains a challenge in carbohydrate chemistry. Since a carboxyl group at the anomeric position and the C-5 hydroxyl group are positioned in 1,4-cis configuration in α-Kdo, which is same as the carboxyl group and the C-5 amino group in α-sialic acid, we envisioned that a 1,5-tethered bicyclic Kdo with α-configuration would ensure complete stereocontrol for α-glycosidation of Kdo. As we expected, bicyclic Kdo donors with bicyclo[10.2.2] to bicyclo[14.2.2] systems were fully α-selective and a donor with bicyclo[13.2.2] system provided the highest glycosidation yield. The bicyclic Kdo donor showed broad substrate scope and allowed for the synthesis of Kdo trimers found in pathogenic bacterial Figure 1. Results in the examination of the glycosidation of bicyclic sialic acid donorsfluorescent probe of lacto-series ganglioside (NeuAcLc4Cer) via the late-stage sialylation5) (Figure 2). Namely, the target molecule was disconnected at the glycosidic linkage between sialic acid and tetraosylceramide in a retrosynthetic manner, affording a 9-trifluoroacetamidosialyl donor and a lacto-tetraosylceramide (Lc4Cer) acceptor, which was designed as a highly TBBz-protected derivative. We successfully constructed the TBBz protected Lc4Cer by block coupling of a GlcNβ(1,3)Gal donor and a glucosyl ceramide acceptor, which was followed by the introduction of Gal at the GlcN of the trisaccharyl ceramide. Then, a bicyclic sialyl donor modified with a trifluoroacetamido group at the C-9 position was glycosidated with the Lc4Cer acceptor to give the framework of NeuLc4Cer in high yield. Finally, subsequent global deprotection and the introduction of a fluorescent dye yielded the target molecule. The fluorescent NeuAcLc4Cer was proven to be useful as an equivalent of natural NeuAcLc4Cer by biophysical evaluations. Single molecule imaging using the fluorescent NeuAcLc4Cer in the live plasma membrane showed the colocalization of ganglioside and CD59 (GPI-anchored protein) known as a raft molecule for approximately 84 ms, 45
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