CHEMICAL AND ENZYMATIC-SYNTHESIS OF MULTIVALENT SIALOGLYCOPEPTIDES

Linear and branched glycopeptides containing multiple sialyl-N-acetyll actosamine side chains have been synthesized using a combined chemical and enzymatic approach. Peptide backbones in which beta-GlcNAc-Asn re sidues were incorporated were obtained in good yields by optimized sol id-phase synthesis following the Boc strategy. The resulting multivale nt glycopeptides were galactosylated in near-quantitative yields using bovine galactosyltransferase, UDP-galactose, and calf alkaline phosph atase that destroys the inhibiting side product UDP. Subsequent enzyma tic sialylation yielded the desired glycopeptides containing asparagin e-linked sialyl-N-acetyllactosamine side chains. The compounds were ch aracterized by H-1 NMR and FABMS. Recombinant sialyltransferase and CM P-sialate synthetase were used for the enzymatic synthesis of sialosid es on a preparative scale. The synthetic glycopeptides were tested as inhibitors of influenza virus to cells, revealing that most of the mul tivalent sialoglycopeptides exhibit increased binding that depends on the spacing when compared to monovalent compounds. A possible mechanis m for increased binding is proposed.