Identification of novel inhibitors of fibroblast growth factor (FGF-2) binding to heparin and endothelial cell survival from a structurally diverse carbohybrid library.
Inhibitors of FGF-2 binding to a heparin-albumin conjugate were identified by ELISA from a library of glucuronic acid derivatives. These compounds were also inhibitors of endothelial cell survival that is dependant on FGF-2 and heparin or heparan sulfate proteoglycans. The results indicate that these bioactive compounds may prove useful as lead structures for the further development of pharmaceutical agents capable of modulating biological activity of FGF-2.
Murphy
Paul V
PV
Department of Chemistry, Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Ireland. paul.v.murphy@ucd.ie
Pitt
Nigel
N
O'Brien
Alan
A
Enright
Philomena M
PM
Dunne
Amanda
A
Wilson
Stephen J
SJ
Duane
Rhona M
RM
O'Boyle
Kathy M
KM
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D016222:Fibroblast Growth Factor 2; D020723:Glucuronic Acid; D006493:Heparin