[Hydrolysis of synthetic peptides by group D cathepsins]

The effects of highly purified preparations of cathepsine D from human liver, spleen and some tumours on synthetic hexa- and heptapeptides were studied. The cathepsins were obtained by repeated chromatography on pepstatin-Sepharose with subsequent gel filtration through Sephadex G-100. The peptides tested were structural analogs of pepstatin, a natural inhibitor of carboxylic proteinases. In these analogs the amino acid statin essential for the inhibitory action was substituted for the residues of natural amino acids serine, threonine and glycine. It was shown that the peptides Ac-Val-Leu-Ser-Leu-Thr, Ac-Val-Val-Ser-Leu-Leu-Ser and Ac-Val-Val-Gly-Leu-Leu-Ser are appropriate substrates for cathepsins D. When leucine was substituted for isoleucine, the peptides were virtually resistant to the action of cathepsins D. The cathepsins from normal liver and spleen hydrolyzed only the peptide bonds formed by leucine. Cathepsins from malignant tumours exhibited a broader specificity in comparison with those from normal tissues, producing slight hydrolysis of other bonds.