In contrast to the processing of folded proHNP1 by the azurophilic proteases, misfolded His 6 -proHNP1 was degraded by these enzymes. These results are consistent with studies demonstrating that Cys substitutions in mutants of RMAD4 [32] , Crp4 [40] and HD5 [39] are protease sensitive compared to the respective native peptides. However, in contrast to the examples cited above, misfolded His 6 -proHNP1B was disulfide-linked but still susceptible to proteolysis. These data demonstrate that the native disulfide motif is essential for proteolytic stability of the proHNP1 as well as the mature peptide.