Galectins are a family of endogenous glycan-binding proteins that have crucial roles in a broad range of physiological and pathological processes. As a group, these proteins use both extracellular and intracellular mechanisms as well as glycan-dependent and independent pathways to reprogramme the fate and function of numerous cell types. Given their multifunctional roles in both tissue fibrosis and cancer, galectins have been identified as potential therapeutic targets for these disorders. Here, we focus on the therapeutic relevance of galectins, particularly galectin 1 (GAL1), GAL3 and GAL9 to tumour progression and fibrotic diseases. We consider an array of galectin-targeted strategies, including small-molecule carbohydrate inhibitors, natural polysaccharides and their derivatives, peptides, peptidomimetics and biological agents (notably, neutralizing monoclonal antibodies and truncated galectins) and discuss their mechanisms of action, selectivity and therapeutic potential in preclinical models of fibrosis and cancer. We also review the results of clinical trials that aim to evaluate the efficacy of galectin inhibitors in patients with idiopathic pulmonary fibrosis, nonalcoholic steatohepatitis and cancer. The rapid pace of glycobiology research, combined with the acute need for drugs to alleviate fibrotic inflammation and overcome resistance to anticancer therapies, will accelerate the translation of anti-galectin therapeutics into clinical practice. 

https://www.nature.com/articles/s41573-023-00636-2.pdf

Targeting galectin-driven regulatory circuits in cancer and fibrosis

The galectin family consists of carbohydrate (glycan) binding proteins that are expressed by a wide variety of cells and bind to galactose-containing glycans. Galectins can be located in the nucleus or the cytoplasm, or can be secreted into the extracellular space. They can modulate innate and adaptive immune cells by binding to glycans on the surface of immune cells or intracellularly via carbohydrate-dependent or carbohydrate-independent interactions. Galectins expressed by immune cells can also participate in host responses to infection by directly binding to microorganisms or by modulating antimicrobial functions such as autophagy. Here we explore the diverse ways in which galectins have been shown to impact immunity and discuss the opportunities and challenges in the field. Galectins can modulate immune cells by binding to glycosylated proteins and lipids on the cell surface, or intracellularly via carbohydrate-dependent or carbohydrate-independent interactions. This Review explores the diverse ways in which galectins affect immunity and discusses the challenges in the field. 

/pdf/the-role-of-galectins-in-immunity-and-infection-3j3zntyg.pdf

The role of galectins in immunity and infection

Innate immune Galectin-7 specifically targets microbes that decorate themselves in blood group-like antigens

http://manuscript.elsevier.com/S0959440X22000732/pdf/S0959440X22000732.pdf

The mannose receptor ligands and the macrophage glycome.

ABO blood group antigens and differential glycan expression: Perspective on the evolution of common human enzyme deficiencies

http://www.jbc.org/article/S0021925822001442/pdf

Galectin-9 recognizes and exhibits antimicrobial activity toward microbes expressing blood group–like antigens

Purification of Recombinant Galectins from Different Species Using Distinct Affinity Chromatography Methods.

Numerous studies have highlighted the utility of glycan microarray analysis for the elucidation of protein-glycan interactions. However, most current glycan microarray studies analyze glycan binding protein (GBP)-glycan interactions at a single protein concentration. While this approach provides useful information related to a GBP’s overall binding capabilities, extrapolation of true glycan binding preferences using this method fails to account for printing variations or other factors that may confound relative binding. To overcome this limitation, we examined glycan array binding of three galectins over a range of concentrations to allow for a more complete assessment of binding preferences. This approach produced a richer data set than single concentration analysis and provided more accurate identification of true glycan binding preferences. However, while this approach can be highly informative, currently available data analysis approaches make it impractical to perform binding isotherms for each glycan present on currently available platforms following GBP evaluation. To overcome this limitation, we developed a method to directly optimize the efficiency of assessing association constants following multi-GBP concentration glycan array analysis. To this end, we developed programs that automatically analyze raw array data (kdMining) to generate output graphics (kaPlotting) following array analysis at multiple doses. These automatic programing methods reduced processing time from 32.8 h to 1.67 min. Taken together, these results demonstrate an effective approach to glycan array analysis that provides improved detail and efficiency when compared to previous methods.

A. Ho

Papers

Galectin-9 recognizes and exhibits antimicrobial activity toward microbes expressing blood group–like antigens

Purification of Recombinant Galectins from Different Species Using Distinct Affinity Chromatography Methods.

An Automated Approach to Assess Relative Galectin-Glycan Affinity Following Glycan Microarray Analysis