Synthesis of a heparan sulfate mimetic disaccharide with a conformationally locked residue from a common intermediate.
A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-D-glucopyranosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy-beta-D-glucopyranose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from D-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.
Fairweather
Jon K
JK
Drug Design Group, Progen Pharmaceuticals Limited, Brisbane, Qld 4066, Australia.
Karoli
Tomislav
T
Liu
Ligong
L
Bytheway
Ian
I
Ferro
Vito
V
D032701:Biomimetics; D002125:Calcium Gluconate / Q000737:chemistry; D003198:Computer Simulation; D004187:Disaccharides / Q000138:chemical synthesis*; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006497:Heparan Sulfate / Q000138:chemical synthesis* / Q000378:metabolism; D008968:Molecular Conformation
D002125:Calcium Gluconate; D004187:Disaccharides; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate