Hepatocyte growth factor fragments that function as potent met receptor agonists and antagonists
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsJennifer R. Cochran, Douglas S. Jones, II, Ping-Chuan Tsai
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Abstract
The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.
Claims19
A variant of human Hepatocyte Growth Factor (hHGF) comprising at least one member selected from an amino acid substitution, an amino acid deletion, an amino acid addition and combinations thereof in the NK1 region, whereby the resulting HGF variant exhibits a characteristic which is a member selected from an affinity for Met greater than that of wild type hHGF, thermal stability greater than that of wild type hHGF, salt stability greater that that of wild-type hHGF, and a combination thereof.
A dimer comprising a first human NK1 (hNK1) variant polypeptide and a second hNK1 variant polypeptide, wherein the first hNK1 variant polypeptide comprises a first linker and the second hNK1 polypeptide comprises a second linker, wherein the first linker comprises at least one cysteine residue and the second linker comprises a moiety reactive with a sulfhydryl group of the cysteine, wherein the dimer is formed by the reaction of cysteine with the moiety reactive with the sulfhydryl group.
Dependencies are inferred from the claim text.