Abstract
Controlling chondroitin sulfates (CSs) biological functions to exploit their interesting potential biomedical applications requires a comprehensive understanding of how the specific sulfate distribution along the polysaccharide backbone can impact in their biological activities, a still challenging issue. To this aim, herein, we have applied an “holistic approach” recently developed by us to look globally how a specific sulfate distribution within CS disaccharide epitopes can direct the binding of these polysaccharides to growth factors. To do this, we have analyzed several polysaccharides of marine origin and semi-synthetic polysaccharides, the latter to isolate the structure-activity relationships of their rare, and even unnatural, sulfated disaccharide epitopes. SPR studies revealed that all the tested polysaccharides bind to FGF-2 (with exception of CS-8, CS-12 and CS-13) according to a model in which the CSs first form a weak complex with the protein, which is followed by maturation to tight binding with kD ranging affinities from ~1.31 μM to 130 μM for the first step and from ~3.88 μM to 1.8 nM for the second one. These binding capacities are, interestingly, related with the surface charge of the 3D-structure that is modulated by the particular sulfate distribution within the disaccharide repeating-units.
Highlights
Chondroitin sulfate (CS) is a family of polysaccharides ubiquitously distributed in the extracellular matrix (ECM) and on cell surfaces usually found attached to proteins in the form of proteoglycans
We carried out a comprehensive analysis of a library of semi-synthetic CSs carrying sulfate groups placed at C-2 and/or
It is important to note that actual knowledge is scarce, recent studies have demonstrated that CS possessing K subunits with 3-O-sulfonated
Summary
Chondroitin sulfate (CS) is a family of polysaccharides ubiquitously distributed in the extracellular matrix (ECM) and on cell surfaces usually found attached to proteins in the form of proteoglycans. These are linear polysaccharides composed of alternating. N-acetylgalactosamine) whose hydroxyl groups can be sulfated in variable positions and quantities, giving rise to different forms of CSs (Figure 1a) [1]. Disulfated (CS-B, CS-D, CS-E, CS-K and CS-L), and even trisulfated disaccharides (CS-M, CS-S and CS-T) have been found in marine species (Figure 1b) [2]. Disulfated (CS-B, CS-D, CS-E, CS-K and CS-L), and even trisulfated disaccharides (CS-M, CS-S and CS-T) have been found in marine species (Figure 1b) [2]. 4.0/).
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