Combinatorial strategies for the discovery of novel protease specificities

This article discusses proven and possible ways to generate novel cleavage specificities in serine proteases using combinatorial mutagenesis, compares the different ways of screening or selecting for desirable mutants, and examines the ways in which combinatorial substrate libraries can be used to gain a more comprehensive insight into protease cleavage preferences. The use of bacteriophage to display both combinatorial protease libraries and combinatorial substrate libraries will be discussed.