[Selectin receptors. 1. Synthesis of SiaLe(a) and SiaLe(x) tetrasaccharides and their polymeric conjugates]

Spacer-armed tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Fuc alpha 1- 4)GlcNAc-sp (SiaLe(a), sp = OCH2CH2CH2NH2) was synthesized from 6-BnGlcNAc-sp with 6-BnAc3GalSEt, Bn3FucSEt, and Ac4Neu5AcSEt methyl ester as glycosyl donors. The final glycosylation of the trisaccharide bearing unprotected 2-, 3-, and 4-hydroxyls of galactose moiety was promoted with NIS-TfOH in MeCN, yield of alpha-sialoside being 48% (29% as the NGlcNAc-SEt derivative). A mixture of beta-connected (2-3) and (2-4) lactones was obtained as a side product (30%). Tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-sp (SiaLe(x)) was synthesized by a similar way starting from 6-Bn-3-MeOBnGlcNAc-sp; yield of alpha-sialylation was 74%, neither N-SEt nor beta-connected lactones were isolated. Condensation of the spacered tetrasaccharides with poly(4-nitrophenylacrylate) gave N-substituted polyacrylamide-type polymers. Biotinylated probes and polymers modified with phosphatidylethanolamine (strong immunogens) were also obtained. The unsubstituted and labelled polymeric derivatives were used for studying selectins and other lectins, as well as production and epitope characterization of monoclonal antibodies against sialooligosaccharides.