Structure-activity relationship of synthesized glucans from Ganoderma lucidum with in vitro hypoglycemic activity

The synthetic polysaccharides, which have precise structure, can be used to design new drugs by comparing structure-activity relationships (SAR). Improved protein stability may be due to the interaction between the polysaccharides and protein, which includes covalent and noncovalent interactions. It is critical to investigate the SAR of polysaccharides with a precise structure from the perspective of protein stability. Glucans-insulin interaction may be a useful stratagy to solve this problem. This study reports the SAR of the synthesized glucan GLSWA-1 and its substructures 2-4 on insulin secretion and discusses its mechanism. The results showed that although GLSWA-1 and its substructures 2-4 bind insulin to varying degrees, compound 2 improves insulin secretion in a dose-dependent manner. Further research found that compound 2 maintains the thermal stability of insulin better than GLSWA-1 through stronger hydrogen bonding, and molecular dynamics simulations demonstrated that compound 2 can form a "groove-binding model" with insulin. This study considerably improves the research on the SAR of glucan based on insulin thermostability and indicates that compound 2, its linear structure, appropriate chain flexibility ((1 → 6)-glucoside bonds), low molecular weight, and smaller steric hindrance is a potential hypoglycemic agent.