Chimeric serine proteases

A method for determining whether a substance has serine protease inhibiting activity, comprising:

• a) combining a chimeric protein with a target substance under conditions such that the chimeric protein exhibits serine protease activity in the absence of the target substance,
• wherein the chimeric protein comprises a first sequence and a second sequence C-terminal to the first sequence and linked to the first sequence by one or more peptide bonds, the first sequence having the amino acid sequence of the first catalytic domain half of a first serine protease and the second sequence having the amino acid sequence of the second catalytic domain half of a second serine protease different from the first serine protease;
• wherein the first sequence has the amino acid sequence of the first catalytic domain half of factor Xa and the second sequence has the amino acid sequence of the second catalytic domain half of trypsin;
• b) measuring the serine protease activity of the chimeric protein in the presence of the target substance and in the absence of the target substance, to detect whether the serine protease activity of the chimeric protein in the presence of the target substance is decreased relative to the serine protease activity of the chimeric protein in the absence of the target substance;
• and
• c) if a decrease in serine protease activity is detected, determining that the target substance has serine protease inhibiting activity.