Scaffold optimization of a tetravalent C-lectin antagonist

C-type lectins constitute a class of proteins able to selectively recognize carbohydrates and bind to polyglycosilated surfaces, which are considered as an interesting pharmaceutical target for their involvement in many physiological and pathological processes.1 In the past few years, in collaboration with the Rojo group (Glycosystems Laboratory, IIQ-CSIC, Sevilla), we demonstrated that two polyester tetravalent dendrons 1a,b functionalized either with pseudo-biomannoside 2 or pseudo-trimannoside 3 ligands (Fig. 1) are good antagonists of the C-lectins DC-SIGN2 and MBL3, which are respectively involved in HIV infection and ischemic reperfusion damage. Despite the promising results obtained both in in vitro and in vivo experiments, the two dendrons showed to suffer from high chemical instability. Here we present the synthesis of two analogous tetraamide dendrons characterized by an optimized scaffold that led to much more stable and still water soluble constructs. Preliminary results of biological assays will also be shown.