Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using β-cyclodextrin as a key scaffold material
Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using β-cyclodextrin as a key scaffold material
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DOI：
10.1016/j.tet.2004.12.035
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发表时间：
2005-02-14
期刊：
影响因子：
2.1
通讯作者：
Nishimura, SI
中科院分区：
文献类型：
--
作者：
Furuike, T;Sadamoto, R;Nishimura, SI
以β-环糊精（beta-CD）为主要原料，采用化学和酶促方法，建立了一种高效、实用的大规模合成具有抗炎活性的7个唾液酸基刘易斯X（SLeX）糖簇的方法。通过与七-6-脱氧-6-碘-β-环糊精和含有一个GlcNAc残基的硫醇钠的偶联反应，制备了一种关键中间体，具有七个N-乙酰基-D-葡糖胺（GlcNAc）残基的β-CD衍生物[（GlcNAc）（7）CD]。随后的（GlcNAc）（7）CD的糖延伸反应在相应的糖核苷酸存在下通过β-1，4-半乳糖基转移酶、α-2，3-唾液酸转移酶和α-1，3-岩藻糖基转移酶V顺利进行（UDP-Gal、CMP-Neu 5Ac和GDP-Fuc），并允许得到单分散的糖树枝状聚合物（M-w = 7924.5，C301 H490 N21 O 196 S7 Na 7的计算值; MALDI-TOF MS，m/z 7946 [M + Na]（+）），其在C-6位完全被7个SLeX支链取代，总产率优异（74%，3步）。利用表面等离子体共振方法，研究了超支化糖树枝状大分子（SLeX）（7）CD对E-选择素与固定在传感器芯片上的SLeXn-BSA相互作用的抑制作用。(C)2004 Elsevier Ltd.保留所有权利。
An efficient and practical method for the large-scale synthesis of an anti-inflammatory glycocluster having seven sialyl Lewis X (SLeX) residues was established on the basis of chemical and enzymatic strategy from beta-cyclodextrin (beta-CD) as a key starting scaffold material. A key intermediate, beta-CD derivative having seven N-acetyl-D-glucosamine (GlcNAc) residues [(GlcNAc)(7)CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-beta-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)(7)CD proceeded smoothly by means of beta-1,4-galactosyltransferase, alpha-2,3-sialyltransferase, and alpha-1,3-fucosyltransferase V in the presence of the corresponding sugar nucleotides (UDP-Gal, CMP-Neu5Ac, and GDP-Fuc) and allowed to give a mono-dispersed glycodendrimer (M-w = 7924.5, calcd for C301H490N21O196S7Na7; MALDI-TOF MS, m/z 7946 [M + Na](+)) that completely substituted with seven SLeX branches at C-6 positions in excellent overall yield (74%, 3 steps). Hyper-branched glycodendrimer, (SLeX)(7)CD, exhibited highly amplified inhibitory effect on the interaction of E-selectin with SLeXn-BSA immobilized on the sensor chip by means of surface plasmon resonance method. (C) 2004 Elsevier Ltd. All rights reserved.