PEGylation of Human Vascular Endothelial Growth Factor.

Vascular endothelial growth factor A-165 (VEGF-A) positively modulates neointimal hyperplasia, lumen stenosis, and neovascularization. One challenge for the use of VEGF-A for potential therapy is its short serum half-life. Therefore, we are designing VEGF-A bioconjugates carrying olythylene lycol (). The purity of the recombinantly expressed human VEGF-A exceeded 90%. The growth factor had a half-maximal effective concentration of 0.9 ng/mL (EC50) and induced tube formation of human umbilical vein endothelial cells. PEGylation was conducted by Schiff base reaction followed by reductive amination. After purification, two species were obtained, with one or two PEG attached per VEGF-A dimer. Both resulting bioconjugates had a purity exceeding 90%, wild-type bioactivity, and increased hydrodynamic radii as required for prolonging the half-life.