Biomedical subjects
Publications and source records attributed to P Holliger.
Bispecific antibodies have immense potential as reagents and in medicine. Until recently, they were made by combining monoclonal antibodies of two different specificities in vitro, or by fusion of the corresponding hybridomas. Protein engineering now offers the chance to construct a range of small 'designer' bispecific antibodies using antibody fragments as building blocks.
Chemical modification studies suggest that two residues of bovine pancreatic ribonuclease A (RNase A), Lys-41 and Asp-121, are important for catalysis. Three mutants of RNase A have been prepared, two point mutants with Lys-41 altered to Arg-41 and Asp-121 altered to Glu-121, and a double mutant where both residues are altered. The Lys-41 Arg mutant has ca. 2% the catalytic activity (kcat/Km) of the native protein, while the Asp-121Glu mutant has ca. 17% the catalytic activity of the native protein. The double mutant has catalytic activity comparable to the Lys-41Arg mutant.
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