The Scripps Research Institute

Elizabeth D Getzoff

John H Griffin

Andrew Gale

Jean-Luc Pellequer

Richard A Lerner

Stephen J Benkovic

Victoria A Roberts

John A Tainer

The present invention relates to methods of introducing one or more cysteine residues into a polypeptide which permit the stabilization of the polypeptide by formation of at least one bond, preferably a disulfide bond, between different domains of the polypeptide. The invention also relates to polypeptides containing such introduced cysteine residue(s), nucleic acids encoding such polypeptides and pharmaceutical compositions comprising such polypeptides or nucleic acids. The invention also relates to vectors, viral particles and host cells containing such nucleic acids, and methods of using them to produce the polypeptides of the invention. Exemplified polypeptides include plasma proteins, including hepatocyte growth factor activator and plasma hyaluronin binding protein, as well as blood coagulation factors, such as Factor VIII, Factor V, Factor XII and prothrombin.

Stabilized proteins with engineered disulfide bonds

The invention describes a metal binding protein capable of forming a coordination complex with a metal cation. The protein contains a sequence of amino acid residues that defines a variable domain of an immunoglobulin light chain having a L1 region and a L3 region, and also contains three contact amino acid residues in the variable domain that participate as ligands for the metal coordination complex.

Metal binding proteins

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San Diego, CA, United States of America

Elizabeth D Getzoff