Glycosaminoglycanomics: where we are

Abstract

Glycosaminoglycans regulate numerous physiopathological processes such as development, angiogenesis, innate immunity, cancer and neurodegenerative diseases. Cell surface GAGs are involved in cell-cell and cell-matrix interactions, cell adhesion and signaling, and host-pathogen interactions. GAGs contribute to the assembly of the extracellular matrix and heparan sulfate chains are able to sequester growth factors in the ECM. Their biological activities are regulated by their interactions with proteins. The structural heterogeneity of GAGs, mostly due to chemical modifications occurring during and after their synthesis, makes the development of analytical techniques for their profiling in cells, tissues, and biological fluids, and of computational tools for mining GAG-protein interaction data very challenging. We give here an overview of the experimental approaches used in glycosaminoglycomics, of the major GAG-protein interactomes characterized so far, and of the computational tools and databases available to analyze and store GAG structures and interactions.

Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System

“…For example, CCL20 interactions with GAGs may be more amenable to inhibition than CCL5 interactions due to the fact that CCL20 is a weakly oligomerizing chemokine [ 159 ] whereas CCL5 interacts with GAGs as a high affinity polymer with multiple redundant epitopes. In any case, success will be dependent on synthetic feasibility, and, fortunately, there has been enormous progress in carbohydrate chemistry in recent years [ 43 , 160 , 161 , 162 ], which may help position GAG mimetics as viable therapeutic entities.…”

Bioprospecting for Exopolysaccharides from Deep-Sea Hydrothermal Vent Bacteria: Relationship between Bacterial Diversity and Chemical Diversity

“…These polysaccharides are polyanionic macromolecules composed of alternating uronic acids and hexosamines or neutral sugars [ 1 , 2 ]. Upon biosynthesis, GAG backbones undergo a series of specific enzymatic reactions leading to a large variety of N - and O -sulfations and epimerization patterns; these molecules are also heterogeneous with respect to size [ 3 ].…”

KnowVolution Campaign of an Aryl Sulfotransferase Increases Activity toward Cellobiose

“…Sulfated GAGs, steroids, and proteins (sulfated tyrosines) play significant roles in signal transduction, blood coagulation, angiogenesis, pathogen invasion, and many more ,. In all cases, sulfate groups attached to the molecules modulate the driving signals to the aforementioned processes .…”

“…Furthermore, the enzymatic degradability of sulfated cellulose is increased due to improved aqueous solubility . The latter properties resulted in an increasing interest for pharmaceutical and biotechnological fields . Regioselective sulfation is important since the sulfation patterns in GAGs are often crucial for their biological functions .…”