abstract |
An aprotinin analogue with reduced nephrotoxicity, wherein, to provide a reduced positive net charge, at least one positively charged amino acid residue outside the protease-binding site is removed or replaced with a neutral or negatively charged amino acid residue, and/or wherein at least one negatively charged amino acid residue is inserted or added, and/or wherein at least one neutral amino acid residue is replaced with a negatively charged amino acid residue, and/or wherein, to provide reduced stability, one or more amino acid residues are deleted, added or replaced with one or more other amino acid residues. |