LANTHANIDE CHELATING CARBOHYDRATE CONJUGATES EMERGE AS SENSITIVE SENSORS TO DETECT AND CHARACTERIZE CARBOHYDRATE-PROTEIN INTERACTIONS

Alvaro Mallagaray 1 Ángeles Canales 2 Álvaro M. Berbís 1 Gema Domínguez 4 Francisco Javier Cañada 1 Sabine André 3 Hans-Joachim Gabius 3 Javier Pérez-Castells 4 Jesús Jiménez-Barbero 1
1Departamento de Biología Físico-Química, Centro de Investigaciones Biológicas-CSIC, Madrid
2Departamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid
3Faculty of Veterinary Medicine, Institute of Physiological Chemistry, Ludwig-Maximilians University, Munich
4Facultad de Farmacia, Departamento de Química, Universidad CEU San Pablo, Madrid

The use of paramagnetic ions with lanthanide binding tags (LBT) for obtaining new NMR parameters with structural information has been extended in the last few years for protein structure determination.1The access to paramagnetic effects has permitted to deduce key conformational and dynamic information in different elegant examples.2

In order to extend this methodology, we have recently reported on the use of a chemically well-defined lanthanide binding tag to perform structural studies of carbohydrates.3

Here we present the application of a 1-b-aminolactose-lanthanide binding tag to the NMR study of carbohydrate-lectin interactions.Paramagnetic effects have been effectively transferred from the carbohydrate to the protein, providing information about location and topological aspects of the protein bound-state. Low affinity ligands or even transient protein-carbohydrate interactions can be detected. Thus, this cutting-edge methodology could be used for screening of competitive inhibitors as well as secondary binding sites.

1Otting, G. Annu. Rev. Biophys.2010,39, 387-405.

2Su, X.; Otting, G.J. Biomol. NMR2010,46, 101-112.

3Pérez-Castells, J. et al.Chem. Commun.2011,47, 7179-7181



 




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