Ag. Gambarini et al., STRUCTURE AND FUNCTION OF FIBROBLAST GROWTH-FACTOR, Brazilian journal of medical and biological research, 29(7), 1996, pp. 835-839
We describe some structural requirements of the fibroblast growth fact
or (FGF) signaling system for the stimulation of the mitogenic respons
e in terms of the design, synthesis and mitogenic activity of linear p
eptides related to the human FGF-1 sequence and the structural require
ments of heparin for the potentiation of the mitogenic activity of FGF
-1. The best mitogenic peptide we have synthesized so far is Ac-WFVGLK
KNGSSKRGPRT-NH2, that has been shown: 1) to bind to heparin-Sepharose
columns with moderate affinity, requiring about 0.5 M NaCl to be elute
d from the resin; 2) to be mitogenic upon BALB/c 3T3 fibroblasts in cu
lture (ED(50) = 10-20 mu M) and 3)to compete with human FGF-1 for cell
ular binding (ID50 = 30-50 mu M) The potentiating activity of heparin
upon FGF-I has shown to be dependent on the oligosaccharide size, degr
ee of sulfation and carboxylation. Apparently, these same requirements
hold for the heparan sulfate molecules. Based on the reported studies
, we propose some important requirements of an oligosaccharide to pote
ntiate FGF-I mitogenic activity: 1) to have a minimum of twelve units,
organized as disaccharides where one of the units is a uronic acid an
d the second is glycosamine; 2) to have at least one iduronic acid sul
fated at position 2 and 3) to have N-sulfated glycosamines, preferenti
ally 6-O-sulfated. To have groups of negative charges is not enough: t
hey need to be localized in a correct conformation.