Heparin Structure and Interactions with Basic Fibroblast Growth Factor

Abstract

Crystal structures of heparin-derived tetra- and hexasaccharides complexed with basic fibroblast growth factor (bFGF) were determined at resolutions of 1.9 and 2.2 angstroms, respectively. The heparin structure may be approximated as a helical polymer with a disaccharide rotation of 174 degrees and a translation of 8.6 angstroms along the helix axis. Both molecules bound similarly to a region of the bFGF surface containing residues asparagine-28, arginine-121, lysine-126, and glutamine-135, the hexasaccharide also interacted with an additional binding site formed by lysine-27, asparagine-102, and lysine-136. No significant conformational change in bFGF occurred upon heparin oligosaccharide binding, which suggests that heparin primarily serves to juxtapose components of the FGF signal transduction pathway.

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release

“…[48][49][50] For angiogenesis stimulation, heparin is often added to induce endothelial cell growth. [51,52] However, high concentrations of heparin inhibit the proliferation of smooth muscle cells. [53] The bFGF bioactivity from PEUU scaffolds without heparin indicated that commonly-used growth factor stabilizing protein BSA [20] alone could stabilize the bFGF and maintain smooth muscle cell mitogenicity.…”

The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP) binds to heparin and cell surfaces via positively charged amino acids in CCP1–2

“…Approaching heparin molecules in solution can therefore bind with only small torsional changes on its stable conformation, which is consistent with previous observations of experimental heparin structures (PDB code 1hpn) or co-crystallysed complexes (eg. PDB codes 1rid, 1bfc and 1e0o) (Faham et al, 1996;Ganesh et al, 2004;Mulloy et al, 1993;Pellegrini et al, 2000).…”

Manipulation of hydrogel assembly and growth factor delivery via the use of peptide–polysaccharide interactions

“…The utility of the assembled heparinized hydrogels in this kind of application is suggested by the fact that heparin binds bFGF to form a stable complex [47,48]. The complex maintains the biological activity of bFGF [49] and can retard bFGF release from polymeric materials [50,51].…”