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Article Dans Une Revue Molecules Année : 2019

Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3

Résumé

Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for beta-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.
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Dates et versions

hal-02408764 , version 1 (18-11-2020)

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Vanya Bogoeva, Miroslav Rangelov, Nadezhda Todorova, Annie Lambert, Clarisse Bridot, et al.. Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3. Molecules, 2019, 24 (24), pp.4561. ⟨10.3390/molecules24244561⟩. ⟨hal-02408764⟩

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