title: A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor.
abstract: Basic fibroblast growth factor (bFGF) is a protein that plays a crucial role in diverse cellular functions, from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Here, we describe the stabilization of bFGF by covalent conjugation with a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors--such as heat, mild and harsh acidic conditions, storage and proteolytic degradation--unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general.
authors: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E Young Drive East, Los Angeles, California 90095, USA.
authors: Thi H
authors: TH
authors: Nguyen
authors: Sung-Hye
authors: SH
authors: Kim
authors: Caitlin G
authors: CG
authors: Decker
authors: Darice Y
authors: DY
authors: Wong
authors: Joseph A
authors: JA
authors: Loo
authors: Heather D
authors: HD
authors: Maynard
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011137:Polystyrenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055550:Protein Stability; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors
chemical_list: D008689:Methacrylates; D011137:Polystyrenes; C524499:polyethylene glycol methacrylate; D016222:Fibroblast Growth Factor 2; D011092:Polyethylene Glycols; C003321:polystyrene sulfonic acid; D006493:Heparin; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1