@article {12521,
	title = {Molecular recognition of a Thomsen-Friedenreich antigen mimetic targeting human galectin-3},
	journal = {ChemMedChem},
	volume = {Aug 9. doi: 10.1002/cmdc.201800525. [Epub ahead of print]},
	year = {2018},
	note = {<p>doi: 10.1002/cmdc.201800525</p>
},
	month = {2018},
	publisher = {Wiley-Blackwell},
	abstract = {<p>Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90\% of adenocarcinomas. Additionally, the binding of the TF-antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction display the potential to prevent cancer metastasis. Herein, a multidisciplinary approach, combining the optimized synthesis of a TF-antigen mimetic with NMR, X-ray crystallography methods and isothermal titration calorimetry assays has been employed to unravel the molecular structural details that govern the Gal-3/TF-mimetic interaction. The TF-mimetic presents a binding affinity for Gal-3 similar to the TF-natural antigen and retains the binding epitope and the bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective a decrease in the enthalpic contribution was observed for the Gal-3/TF-mimetic complex, however this behaviour is compensated by a favourable entropy gain. From a structural perspective, these results establish our TF-mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and likely be used to hamper Gal-3-mediated cancer cells adhesion and metastasis.</p>
},
	keywords = {galectin-3, molecular recognition, NMR spectroscopy, Tumour-associated carbohydrate antigens, X-ray crystallography},
	isbn = {1860-7179},
	url = {https://doi.org/10.1002/cmdc.201800525},
	author = {Santarsia, Sabrina and Grosso, Ana Sofia and Trov{\~a}o, Filipa and Jes{\'u}s Jim{\'e}nez-Barbero and Carvalho, Ana Lu{\'\i}sa and Nativi, Cristina and Marcelo, Filipa}
}
