Galectins are a family of galactoside-specific lectins that are involved in a myriad of metabolic and disease processes. Due to roles in cancer and inflammatory and heart diseases, galectins are attractive targets for drug development. Over the last two decades, various strategies have been used to inhibit galectins, including polysaccharide-based therapeutics, multivalent display of saccharides, peptides, peptidomimetics, and saccharide-modifications. Primarily due to galectin carbohydrate binding sites having high sequence identities, the design and development of selective inhibitors targeting particular galectins, thereby addressing specific disease states, is challenging. Furthermore, the use of different inhibition assays by research groups has hindered systematic assessment of the relative selectivity and affinity of inhibitors. This review summarises the status of current inhibitors, strategies, and novel scaffolds that exploit subtle differences in galectin structures that, in conjunction with increasing available data on multiple galectins, is enabling the feasible design of effective and specific inhibitors of galectins. small-molecule crystallography, University of London, UK) undertook post-doctoral research in protein X-ray crystallography and drug-design in academia and industry within Canada, USA, Switzerland and Australia. In 2002 Helen established a protein X-ray crystallography structural biology group at the Institute for Glycomics, Griffith University. As recognition of her international contribution to structural biology and chemistry she was admitted as fellow of the Royal Society of Chemistry (FRSC) in 2006. Her research involves determination of atomic protein structure, analysis of protein-ligand interactions and application of this information in understanding protein function and for structure based drug-design. Her research group has a major focus on lectins critical to disease progression including her research program on galectins that have importance in serious conditions including cancer. Khuchtumur Bum-Erdene completed his Bachelors degree in Chemistry (

Galectin-3 is a β-galactoside-specific, carbohydrate-recognizing protein (lectin) that is strongly implicated in cancer development, metastasis, and drug resistance. Galectin-3 promotes migration and ability to withstand drug treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Due to high amino acid conservation among galectins and the shallow nature of their glycan-binding site, the design of selective potent antagonists targeting galectin-3 is challenging. Herein, we report the design and synthesis of novel taloside-based antagonists of galectin-3 with enhanced affinity and selectivity. The molecules were optimized by in silico docking, selectivity was established against four galectins, and the binding modes were confirmed by elucidation of X-ray crystal structures. Critically, the specific inhibition of galectin-3-induced BCP-ALL cell agglutination was demonstrated. The compounds decreased the viability of ALL cells even when grown in the presence of protective stromal cells. We conclude that these compounds are promising leads for therapeutics, targeting the tumor-supportive activities of galectin-3 in cancer.