IMPROVED ENZYMATIC-SYNTHESIS OF A HIGHLY POTENT OLIGOSACCHARIDE ANTAGONIST OF L-SELECTIN

The polylactosamine sLex beta 1-3'(sLex beta 1-6')LacNAc beta 1-3'(sLe x beta 1-6')LacNAc beta 1-3'(sLex beta 1-6' (7) (where sLex is Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc and LacNAc is Gal beta 1-Gl cNAc) is a nanomolar L-selectin antagonist and therefore a potential a nti-inflammatory agent (Renkonen et al, (1997) Glycobiology, 7, 453), Here we describe an improved synthesis of 7, The octasaccharide LacNAc beta 1-3'LacNAc beta 1-3'LacNAc beta 1-3'LacNAc (4) was converted int o the triply branched undecasaccharide LacNAc beta 1-3'(GlcNAc beta 1- 6')LacNAc beta 1-3' (GlcNAc beta 1-6')LacNAc beta 1-3'(GlcNAc beta 1-6 ')LacNAc (5) by incubation with UDP-GlcNAc and the midchain beta 1,6-G lcNAc transferase activity of rat serum, Glycan 5 was enzymatically be ta 1,4-galactosylated to LacNAc beta 1-3'(LacNAc beta 1-6')LacNAc beta 1-3'(LacNAc beta 1-6')LacNAc beta 1-3'(LacNAc beta 1-6')LacNAc (6), C ombined with the enzymatic conversion of 6 to 7 (Renkonen et al., loc. cit,) and the available chemical synthesis of 4, our data improve the availability of 7 for full assessment of its anti-inflammatory proper ties. (C) 1997 Federation of European Biochemical Societies.