Galectin-3 (Gal-3), an endogenous lectin, is ubiquitously expressed in various mammalian tissues. It is a member of the galectin family and is characterized by a carbohydrate recognition domain that has affinity for β-galactoside structures. This interaction mediates the binding of Gal-3 to many glycoproteins and glycolipids in the cell membrane, including integrins, EGFR, transforming growth factor beta receptorand others. This variety of ligands allows Gal-3 to be implicated in a wide spectrum of physiological and pathological processes, such as cancer. Importantly, as Gal-3 is identified as a key player in different stages of cancer progression, it has been identified as a valuable therapeutic target in the fight against cancers. However, commercially available anti-Gal-3 therapeutic reagents are lacking. It poses an urgent need for the development of inhibitors that specifically target Gal-3. In previous reports, we isolated a 20.5 kDa arabinogalactan polysaccharide, RN1, from the flowers of Panax notoginseng. It markedly inhibits pancreatic ductal adenocarcinoma (PDAC) cells growth in vitro, in vivo and in patient-derived xenografts. Mechanistically, RN1 band to Gal-3, suppressed Gal-3 expression and inactivated Gal-3-associated signaling pathways. According to these results, our further step is to modify this polysaccharide or find other analogues targeting Gal-3 to develop a novel and stronger Gal-3 inhibitor as a potential candidate for human PDAC treatment. Here, we choose dendrimers as scaffold to bind multivalent lactose to increase the bind affinity between lactose and Gal-3. By controlling the reaction condition, the size of dendrimer and the molar ratio of dendrimers and lactose, we synthesize a series of lactose- based dendrimers. The functionalized dendrimers were characterized by MALDI-TOF-MS. Additional characterization details were provided by H NMR spectra. SPR results indicated that the lactose- based dendrimer with higher degree of substation had stronger bind affinity to Gal-3. In our further study, we will evaluate the anti-pancreatic cancer activity of these lactose-based dendrimer in vitro and in vovo to look forward a stronger Gal-3 inhibitor as potential drug candidate to treatment PDAC cancer.

Synthesis of multivalent lactose-based dendrimers and their antitumor activity by targeting galectin-3

254th National Meeting (2017)

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