脂質抱合ヘパラン硫酸模倣体の合成とその補体阻害効果

Heavily sulfated clusters of maltose are designed as mimetics of heparan sulfate (HS), exhibiting diverse biological activity properties of HS. Herein, the synthesis of three function-spacer-lipid (FSL) constructs containing mono, di, and tri sulfated maltoses is reported. FSLs are a class of synthetic glycolipids, the key features of which are simplicity of synthesis and capacity to integrate into cell membranes with sustained retention. A copper-catalyzed azide-alkyne cycloaddition click reaction is employed for the conjugation of the sulfated maltose entities with the respective spacer-lipid block because acylation with activated esters failed to provide the desired products. One FSL construct, featuring a single sulfated maltose unit conjugated to the lipid, demonstrated dose-dependent inhibition of complement activation in a cellular system, with maximal efficacy observed at 15 µg mL^-1. These findings highlight the potential of FSL-based HS mimetics for modulating immune responses.