Interaction of Siglec-4 with naturally occurring and synthetic glycoconjugates

The aim of this work has been to provide insights into the structure-function relationship of Siglec-4 binding naturally occurring sialic acids as well as synthetic sialic acid derivatives. Structural information of the Siglec binding site and its interactions with glycoconjugates were obtained from homology modeling of the sialic acid binding domain and molecular docking calculations with several sialosides. Furthermore, the interaction of chemically synthesized sialic acid derivatives with improved inhibitory potential for Siglec-4 as well as the interactions of Siglec-2 and Siglec-4 with oligo- and even polyvalent sialoglycoconjugates occurring in bovine milk are described. Finally, the potential of enzymatic sialylation using trans-sialidases from Trypanosoma congolense has been investigated demonstrating that trans-sialidases can sialylate glycoproteins like asialofetuin to sufficiently high density for Siglec-4 recognition.