Chemical Lectinology: Tools for Probing the Ligands and Dynamics of Mammalian Lectins In Vivo

Abstract

Summary The importance and complexity associated with the totality of glycan structures, i.e. the glycome, has garnered significant attention from chemists and biologists alike. However, what is lacking from this biochemical picture is how cells, tissues, and organisms interpret glycan patterns and translate this information into appropriate responses. Lectins, glycan-binding proteins, are thought to bridge this gap by decoding the glycome and dictating cell fate based on the underlying chemical identities and properties of the glycome. Yet, our understanding of the in vivo ligands and function for most lectins is still incomplete. This review focuses on recent advances in chemical tools to study the specificity and dynamics of mammalian lectins in live cells. A picture emerges of lectin function that is highly sensitive to its organization, which in turn drastically shapes immunity and cancer progression. We hope this review will inspire biologists to make use of these new techniques and stimulate chemists to continue developing innovative approaches to probe lectin biology in vivo.

A Novel Therapeutic Strategy for Pancreatic Cancer: Targeting Cell Surface Glycan Using rBC2LC-N Lectin–Drug Conjugate (LDC)

“…In contrast to the general concept, the extent of lectin hemagglutination activity is quite variable (10). More than 100 putative endogenous lectins, such as selectin and galectin (11), have been identified in humans (12) and contribute to various physiological processes (10).…”

pH-Degradable Mannosylated Nanogels for Dendritic Cell Targeting

“…By contrast, the latter can be obtained through the use of socalled synthetic glycopolymers that exist of monomeric carbohydrate-bearing repeating units. 12,13 With regard to immuno-therapy, there is a strong rationale for delivering vaccine antigens and immune-stimulatory cues to DCs in nanoparticulate form. [14][15][16] Relative to soluble antigens, antigens formulated as nanoparticles promote cross-presentation to CD8 + T-cells that can differentiate into cytotoxic T-cells that can recognize and eliminate infected and malignant cells.…”

Isotope-targeted glycoproteomics (IsoTaG) analysis of sialylated N- and O-glycopeptides on an Orbitrap Fusion Tribrid using azido and alkynyl sugars

“…Until recently, cancer glycosylation was largely characterized at the level of global cell surface abundance using lectins, antibodies, or related detection reagents [11,12]. A more detailed structural analysis of cancer glycoproteomes has been challenging due to the complex and heterogeneous nature of glycosylation [13,14].…”