Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1. - Archive ouverte HAL Access content directly
Journal Articles Glycobiology Year : 2014

Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1.

Juan C Muñoz-García
  • Function : Author
M José García-Jiménez
  • Function : Author
Paula Carrero
  • Function : Author
Angeles Canales
  • Function : Author
Jesús Jiménez-Barbero
  • Function : Author
Manuel Martín-Lomas
  • Function : Author
José L de Paz
  • Function : Author
Jesus Angulo
Hugues Lortat-Jacob
  • Function : Author
  • PersonId : 970500
Pedro M Nieto
  • Function : Author


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 the sulfation pattern and in the 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 of 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.

Dates and versions

hal-01065053 , version 1 (17-09-2014)



Juan C Muñoz-García, M José García-Jiménez, Paula Carrero, Angeles Canales, Jesús Jiménez-Barbero, et al.. Importance of the polarity of the glycosaminoglycan chain on the interaction with FGF-1.. Glycobiology, 2014, 24 (11), pp.1004-1009. ⟨10.1093/glycob/cwu071⟩. ⟨hal-01065053⟩
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