Aggregation Pathway of Recombinant Human Keratinocyte Growth Factor and Its Stabilization

摘要: Recombinant human keratinocyte growth factor (rhKGF) is prone to aggregation at elevated temperatures. Its pathway proposed proceed initially with a conformational change which perhaps results from repulsion between positively charged residues in clusters forming heparin binding sites. Unfolding of the protein leads formation large soluble aggregates. These aggregates then form disulfide cross-linked precipitates. Finally these precipitates are converted scrambled disulfides and/or non-disulfide Stabilizers such as heparin, sulfated polysaccharides, anionic polymers and citrate can greatly decrease rate rhKGF molecules may all act by reducing charge on thus stabilizing native conformation. EDTA, other hand, found inhibit has only moderate effect rhKGF.