LAUSR

Sialoglycans play a key role in many biological recognition processes and sialylated conjugates of various types have successfully been applied, e.g., as antivirals or in anti-tumor therapy. A key feature for high affinity binding of such conjugates is the multivalent presentation of sialoglycans which often possess synthetic challenges. Here, we describe the combination of solid phase polymer synthesis and enzymatic sialylation yielding 3'-sialyllactose-presenting precision glycomacromolecules. CMP-Neu5Ac synthetase from Neisseria meningitidis (NmCSS) and sialyltransferase from Pasteurella multocida (PmST1) were combined in a one-pot reaction giving access to sequence-defined sialylated macromolecules. Surprisingly, when employing Tris(hydroxymethyl)aminomethane (Tris) as a buffer, formation of significant amounts of α-linked Tris-sialoside was observed as a side reaction. Further exploring and exploiting this unusual sialylation reaction, different neoglycosidic structures were synthesized showing that PmST1 can be used to derive both, sialylation on natural carbohydrates as well as on synthetic hydroxylated scaffolds. This article is protected by copyright. All rights reserved.