Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis

Abstract

We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF165, HB-EGF, and FGF2. Notably, GlcNHAc(6-O-SO3−)-IdoA(2-O-SO3−) (HT-2,6S-NAc) tetrasaccharide showed strong binding with the VEGF165 growth factor. In vitro vascular endothelial cell proliferation, migration and angiogenesis was inhibited in the presence of VEGF165 and HT-2,6S-NAc or HT-6S-NAc, revealing the potential therapeutic role of these synthetic HS ligands.