Abstract: The present invention provides a biologically active multimeric polypeptide molecule in which two or more monomeric subunits are linked together as a single polypeptide ("fusion multimer"). These fusion multimers are more easily and rapidly refolded than unfused multimers, because the reactions necessary to generate the biologically active multimeric form of the polypeptide proceed with first order, rather than second or higher order, reaction kinetics. Fusion multimers also eliminate the simultaneous formation of undesired polypeptide by-products during refolding. The fusion multimers of the present invention specifically include PDGF fusion dimers.

Abstract: Provided are hybrid receptor molecules wherein one domain of the receptor is derived from the cytokine superfamily of receptors and other domain is derived from a heterologous family of receptors. Also provided are methods for identifying ligands that bind to the hybrid receptor molecules.

Abstract: A method for refolding recombinant platelet-derived growth factor from a high expression host cell system, such as E. coli, is provided in accordance with the present invention. The recombinant platelet-derived growth factor is isolated from inclusion body proteins, after which the free sulfydryl groups of the reduced monomeric recombinant protein are blocked. The blocked recombinant protein can then be brought into a biologically active conformation, without interference from the formation of incorrect disulfide bonds. Once in a biologically active conformation, the recombinant platelet-derived growth factor may be unblocked to allow the desired disulfide bonds to form, thus locking the recombinant protein into a biologically active conformation. The present invention also provides a novel mixed disulfide intermediate wherein the free sulfhydryl groups of reduced recombinant platelet-derived growth factor are derivatized to a disulfide blocking agent.

Abstract: Novel platelet-derived growth factor (PDGF) analogs are provided in accordance with the present invention. Also provided is a method for the production of homogeneous quantities of these novel analogs. The novel analogs of the present invention, when refolded, have substantially the same biological activity as naturally occurring PDGF B.sub.109. The method of the present invention employs the use of a stop codon on the c-sis gene, or other coding sequence for a precursor protein of PDGF B.sub.109, or analogs thereof, at a position corresponding to a location from about amino acid 111 to about amino acid 160. The method of the present invention results in the production of relatively large homogeneous quantities of recombinant PDGF B analogs from high expression host cells, such as E. coli.

Abstract: Monoclonal antibodies specific for epitopes found on the B chain of PDGF (including v-sis, c-sis and platelet-derived forms) may be bound to columns and used for purification of rPDGF B. A solution containing a polypeptide possessing at least part of the structural conformation of rPDGF B is passed over such a column and the rPDGF B is bound to the antibody. The rPDGF B may then be eluted from the column to yield rPDGF B of greater than 95% purity as determined by SDS-PAGE.

Abstract: Novel platelet-derived growth factor (PDGF) analogs are provided in accordance with the present invention. Also provided is a method for the production of homogeneous quantities of these novel analogs. The novel analogs of the present invention, when refolded, have substantially the same biological activity as naturally occurring PDGF B.sub.109. The method of the present invention employs the use of a stop codon on the c-sis gene, or other coding sequence for a precursor protein of PDGF B.sub.109, or analogs thereof, at a position corresponding to a location from about amino acid 111 to about amino acid 160. The method of the present invention results in the production of relatively large homogeneous quantities of recombinant PDGF B analogs from high expression host cells, such as E. coli.