A holistic approach to unravelling chondroitin sulfation: Correlations between surface charge, structure and binding to growth factors.

Graphical abstract Highlights • Chondroitin sulfate (CS) derivatives sulfation-dependently bind growth factors. • The disposition of the sulfates modulates the surface charge of the helical structure. • O-6 sulfation favours the arrangement of sulfates on the surface. • High-sulfated CS variants on the surface enhance the binding capacity. Abstract Chondroitin sulfate (CS) is a relevant family of polysaccharides that participates in a large variety of biological events that are related to neural processes by regulating various growth factors through the pattern and degree of sulfation of the polysaccharide. However, their own complexity makes their optimization for biomedical applications a difficult undertaking. Thus, a different perspective has to be taken. Herein, we show that the particular sulfate distribution within the disaccharide repeating-unit plays a key role in the binding of growth factors (GFs). In particular, this disposition modulates the surface charge of the helical structure that, interestingly, has a significant influence on the binding capacity of CSs with several GFs. This fact should be carefully considered in the design of new ligands with improved activity as GFs ligands. [ABSTRACT FROM AUTHOR]