Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes.

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3'-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity.

Innovation Analysis on Postgenomic Biomarkers: Glycomics for Chronic Diseases.

Despite decades of investment in biomarker research, we still do not have robust and field-tested biomarkers for many chronic diseases so as to anticipate clinical outcomes and thus move toward personalized medicine. Biomarker innovations have tended to focus on genomics, but next-generation biomarkers from the nascent field of glycomics now offer fresh vistas for innovation in chronic disease biomarkers and systems diagnostics. Glycosylation, regarded as a complex enzymatic process where sugars (glycans) bind to proteins and lipids, affects many human biological functions, including cell signaling, adhesion, and motility. Notably, and contrary to proteins, glycan biosynthesis does not require a template; rather its final structure is catalyzed by a repertoire of enzymes that attach or detach monosaccharides in the glycosylation pathway, making glycomics research more challenging than proteomics or genomics. Yet, given glycans' biological significance, alterations in their processing may be detrimental to human health and also offer insights for preventive medicine and wellness interventions. Therefore, studying glycans' structure and understanding their function and molecular interactions in the emerging field of glycomics are key to unraveling the pathogenesis of various common chronic diseases. This review summarizes the major concepts in glycomics, including glycan release methods, techniques for large-scale glycan analysis, and glycoinformatic tools for data handling and storage. In all, this analysis on glycomics offers strategies to build a robust postgenomic innovation roadmap for glycan-driven biomarkers as the field is anticipated to mature further and gain greater prominence in the near future.