| 摘要 |
The invention provides an isolated polypeptide including an immunoglobulin C<SUB>H</SUB>3 region domain polypeptide, or functional fragment thereof, having at least one Pro to GIy substitution and exhibiting enhanced stability, including an enhanced folding rate, compared to an unsubstituted C<SUB>H</SUB>3 domain, wherein the at least one Pro to GIy substitution comprises C<SUB>H</SUB>3 residue Pro38 or a C<SUB>H</SUB>3 domain equivalent thereof. Multimeric complexes of an immunoglobulin C<SUB>H</SUB>3 region domain polypeptide, or functional fragment thereof, having at least one Pro to GIy substitution with a second immunoglobulin C<SUB>H</SUB>3 region domain polypeptide also are provided by the invention. The multimeric complexes can include antibodies, antibody functional fragments such as Fd, Fv, Fab, F(ab'), F(ab)<SUB>2</SUB>, F(ab')<SUB>2</SUB>, single chain Fv (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies or minibody and other binding polypeptides having an immunoglobulin C<SUB>H</SUB>3 region domain polypeptide such as a peptibody or an Fc fusion polypeptide. An isolated population of polypeptides including a plurality of immunoglobulin C<SUB>H</SUB>3 region domain polypeptides, or functional fragments thereof, is further provided. Each C<SUB>H</SUB>3 region domain polypeptide within the populations includes at least one Pro to GIy substitution and exhibits enhanced stability, including an enhanced folding rate, compared to an unsubstituted C<SUB>H</SUB>3 domain, wherein the at least one Pro to GIy substitution comprises C<SUB>H</SUB>3 residue Pro38 or a C<SUB>H</SUB>3 domain equivalent thereof. The invention further provides a method of producing a multimeric binding polypeptide and a method of treating a pathological condition characterized by aberrant cell growth. |
