Oligolysine-based saccharide clusters: synthesis and specificity

Area of Science:

• Carbohydrate Chemistry
• Glycobiology
• Bioconjugation

Background:

• Cell surface receptors, particularly membrane lectins, play crucial roles in biological processes.
• Developing specific and selective carbohydrate ligands is essential for understanding and manipulating these interactions.

Purpose of the Study:

• To synthesize and characterize novel homogeneous glycoclusters with multiple disaccharide units.
• To evaluate the binding affinity and selectivity of these glycoclusters towards plant lectins and cell surface lectins.

Main Methods:

• Disaccharides (lactose, dimannoses) were conjugated to peptide cores via amide bonds, forming glycosyl-pyroglutamyl-beta-alanine derivatives.
• Oligolysine peptides (Lys(n)-Ala-Cys-NH2, n=1-5) were fully substituted with these derivatives.
• Fluorescent tagging was achieved using fluorescein iodoacetamide on the cysteine thiol group.
• Binding affinities were measured using surface plasmon resonance (SPR).
• Cellular uptake selectivity was assessed by flow cytometry using HepG2 cells and monocyte-derived dendritic cells.

Main Results:

• Homogeneous glycoclusters with varying numbers of disaccharide units were successfully synthesized.
• Glycoclusters with four or five disaccharide units exhibited high affinity and narrow selectivity for plant lectins.
• These multivalent glycoclusters demonstrated selective binding to specific cell surface membrane lectins (galactose-specific on HepG2, mannose-specific on dendritic cells).

Conclusions:

• Multivalent glycoclusters are effective tools for targeting specific lectin interactions.
• The synthesized glycoclusters offer a promising platform for applications in diagnostics and therapeutics requiring precise cell targeting.