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 β-cyclodextrin (β-CD) as a key starting scaffold material. A key intermediate, β-CD derivative having seven N-acetyl-d-glucosamine (GlcNAc) residues [(GlcNAc)7CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-β-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)7CD proceeded smoothly by means of β-1,4-galactosyltransferase, α-2,3-sialyltransferase, and α-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 (Mw=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)7CD, 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.