Synthesis of structurally defined chondroitin sulfate: Paving the way to the structure-activity relationship studies

Chondroitin sulfate (CS) is one of the major and widespread glycosaminoglycans, a family of structurally complex, linear, anionic hetero-co-polysaccharides. CS plays a vital role in various normal physiological and pathological processes, thus, showing varieties of biological activities, such as anti-oxidation, anti-atherosclerosis, anti-thrombosis, and insignificant immunogenicity. However, the heterogeneity of the naturally occurring CS potentially leads to function unspecific and limits further structure-activity relationship studies. Therefore, the synthesis of CS with well-defined and uniform chain lengths is of major interest for the development of reliable drugs. In this review, we examine the remarkable progress that has been made in the chemical, enzymatic and chemoenzymatic synthesis of CS and its derivatives, providing a broad spectrum of options to access CS of well controlled chain lengths.