Variants of vascular endothelial cell growth factor having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids

Abstract

The present invention involves the preparation of vascular endothelial growth factor (VEGF) antagonist molecules comprising variant VEGF polypeptides which are capable of binding to and occupying cell surface VEGF receptors without inducing a VEGF response, thereby antagonizing the biological activity of the native VEGF protein. Specifically, the variant VEGF polypeptides of the present invention comprise modifications of at least one cysteine residue in the native VEGF sequence, thereby inhibiting the ability of the variant polypeptide to dimerize through the formation of disulfide bonds. The present invention is further directed to methods for preparing such variant VEGF antagonists and to methods, compositions and assays utilizing such variants for producing pharmaceutically active materials having therapeutic and pharmacologic properties that differ from the native VEGF protein.