Higher doses increase the selection pressure for single site mutations that confer resistance, as all strains but those that carry the mutation will be eliminated, and thus the resistant strain will propagate.

Conclusion Single site mutations within the segment Asp355-Arg356-Pro357 of PAI-1 yield Gdn-HCl activatable inhibitors that can still form SDS stable complexes with plasminogen activators, with second order inhibition constants that are similar to the native inhibitor.