Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1
|Author/s||Muñoz García, Juan Carlos
García Jiménez, M. José
Jiménez Barbero, Jesús
Martín Lomas, Manuel
Paz, José L. de
Angulo Álvarez, Jesús
Lortat Jacob, Hughes
Nieto, Pedro M.
|Abstract||Heparin-like saccharides play an essential role in binding to the fibroblast growth factor (FGF)-1 and to their membrane receptors fibroblast growth factor receptor forming a ternary complex that is responsible of the ...
Heparin-like saccharides play an essential role in binding to the fibroblast growth factor (FGF)-1 and to their membrane receptors fibroblast growth factor receptor forming a ternary complex that is responsible of the internalization of the signal, via the dimerization of the intracellular regions of the receptor. In this study, we report the binding affinities between five synthetic hexasaccharides with human FGF-1 obtained by surface plasmon resonance experiments, and compare with the induced mitogenic activity previously obtained. These five oligosaccharides differ in sulfation pattern and in sequence. We have previously demonstrated that all the five hexasaccharides have similar 3D structure of the backbone. Consequently, the differences in binding affinity should have their origin in the substitution pattern. Subsequently, the different capacity for induction of mitogenic activity can be, at least partially, explained from these binding affinities. Interestingly, one of the oligosaccharides lacking axially symmetry (3) was biologically inactive, whereas the other (2) was the most active. The difference between both compounds is the order of the FGF-binding motifs along the chain relative to the carbohydrate polarity. We can conclude that the directionality of the GAG chain is essential for the binding and subsequent activation. The relative biological activity of the compounds with regular substitution pattern can be inferred from their values of IC50. Remarkably, the sulfate in position 6 of d-glucosamine was essential for the mitogenic activity but not for the interaction with FGF-1.
|Citation||Muñoz García, J.C., García Jiménez, M.J., Carrero, P., Canales, Á., Jiménez Barbero, J., Martín Lomas, M.,...,Nieto, P.M. (2014). Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1. Glycobiology, 24 (11), 1004-1009.|