Application of Schiff base copper(II) and iron(III) chelates to site-specific cleavage of a trypsin.

Amidine-containing Schiff base iron(III) and copper(II) chelates were prepared from alpha-amino acid, metal ion, and salicylaldehyde. These chelates behaved as specific inhibitors of trypsin, with Ki values in the range 10(-5)-10(-6) M. Selective cleavage of the trypsin backbone resulting from specific binding of the chelate to the trypsin active site was investigated. Cleavage was observed when trypsin was incubated with amidine-containing copper(II) or iron(III) chelate, H2O2, and ascorbate. Examination of the three-dimensional structure of trypsin suggests that cleavage occurred at a peptide bond within the Gly195-Ala204 sequence.