A focused sulfated glycoconjugate Ugi library for probing heparan sulfate-binding angiogenic growth factors

作者：Liu Ligong^*; Li Caiping; Cochran Siska; Feder Daniel; Guddat Luke W; Ferro Vito

来源：Bioorganic & Medicinal Chemistry Letters, 2012, 22(19): 6190-6194.

DOI：10.1016/j.bmcl.2012.08.001

• Growth factors
• Ugi condensation
• Heparan sulfate mimetics
• Glycoconjugates
• Inhibitors

A library of small molecule heparan sulfate (HS) mimetics was synthesized by employing the Ugi four-component condensation of D-mannopyranoside-derived isocyanides with formaldehyde as the carbonyl component and a selection of carboxylic acids and amines, followed by sulfonation. The library was used to probe the subtle differences surrounding the ionic binding sites of three HS-binding angiogenic growth factors (FGF-1, FGF-2 and VEGF). Each compound features 3 or 4 sulfo groups which serve to anchor the ligand to the HS-binding site of the protein, with a diverse array of functionality in place extending from C-1 or C-6 to probe for adjacent favorable binding interactions. Selectivity of binding to these proteins was clearly observed and supported by molecular docking calculations.

• 出版日期2012-10-1