Synthetic Mucin‐Like Glycopeptides as Versatile Tools to Measure Effects of Glycan Structure/Density/Position on the Interaction with Adhesion/Growth‐Regulatory Galectins in Arrays

Abstract

Functional pairing of cellular glycoconjugates with tissue lectins is a highly selective process, whose determinative factors have not yet been fully delineated. Glycan structure and modes of presentation, that is, its position and density, can contribute to binding, as different members of a lectin family can regulate degrees of responsiveness to these factors. Using a peptide repeat sequence motif of the glycoprotein mucin-1, the principle of introducing synthetic (glyco)peptides with distinct variations in these three parameters to an array-based screening of tissue lectins is illustrated. Interaction profiles of seven adhesion/growth-regulatory galectins cover the range from intense signals with core 2 pentasaccharides and core 1 binding for galectins-3 and -5 to a lack of binding for galectin-1 and also the galectin-related protein, which was included as a negative control. Remarkably, the two tandem-repeat-type galectins-4 and -8 were distinguished by core 1 sialylation, as the two separated domains were. These results encourage further synthetic elaboration of the glycopeptide library and testing of the network of natural galectins and rationally engineered variants of the lectins.

Network analysis of adhesion/growth‐regulatory galectins and their binding sites in adult chicken retina and choroid

“…; Artigas et al. ). This possibility gives a reason to link this part with the analysis of lectin presence.…”

“…Of note, in most instances (except for a2,6-sialylated glycans without at least one LacNAc repeat), the listed glycans have reactivity with galectins. This has been documented with neoglycoproteins that present synthetic N-glycans, free oligosaccharides using isothermal titration calorimetry, frontal affinity chromatography or arrays with O-glycans (Andr e et al 1997(Andr e et al , 2004(Andr e et al , 2007Ahmad et al 2002;Hirabayashi et al 2002;Unverzagt et al 2002;Stowell et al 2008;Rapoport et al 2015;Artigas et al 2017). This possibility gives a reason to link this part with the analysis of lectin presence.…”

Sensing Glycans as Biochemical Messages by Tissue Lectins: The Sugar Code at Work in Vascular Biology

“…Dense clustering favours binding of galectins-3 and -4. 180,181 Its sialylation in α2,3linkage renders binding to galectin-8 130 and siglecs, especially sialoadhesin (siglec-1) 182 and siglec-9, 183 possible, disialylation (at the Gal and GalNAc moieties) to siglec-4. 184 In the framework of the system of O-glycosylation, the α2,3-sialyla-tion of the core 1 disaccharide precludes its branching to yield core 2 glycans, as core 1 disaccharide synthesis makes core 4 production impossible (►Fig.…”

“…Decisions between routes of synthesis explain how growth-regulatory processes are switched on or off. 181,188,189 The role as a metastasis suppressor of the glycosyltransferase N-acetylgalactosaminide α2,6-sialyltransferase-2 (ST6GalNAcT-2) in breast cancer had been attributed to reduced T(F) disaccharide presence that lowers breast tumour cell aggregation and retention at metastatic sites via galectin-3. 190 Effectively, this type of α2,6-sialylation diverts product generation from reaching, for example, core 1 to sT n , as shown in ►Fig.…”

Presentation Mode of Glycans Affect Recognition of Human Serum anti-Neu5Gc IgG Antibodies

“…Several studies investigated the importance of glycan density for avidity and selectivity of antibodies and lectins in a variety of controllable multivalent systems. [11][12][13][14][15][16] For example, modulation of glycan densities on a carrier protein (e.g., bovine serum albumin or BSA) revealed different binding patterns of serum antibodies, 9 and similarly affected binding preferences of antibodies and lectins against dendrimers 17 and synthetic polymer 13 with different glycan densities.…”