Chemical and enzymatic synthesis of glycocluster having seven sialyl lewis X arrays using β-cyclodextrin as a key scaffold material

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.