Effect of Cathepsins D from Normal and Malignant Tissues on Synthetic Peptides

• Published in: The Journal of biological chemistry Vol. 247; no. 13; pp. 4224 - 4228
• Main Authors: Kazakova, Olga V., Orekhovich, Vassiliy N., Pourchot, Linda, Schuck, James M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.07.1972; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acids; Aminopeptidases; Animals; Binding Sites; Cathepsins - antagonists & inhibitors; Dicarboxylic Acids; Hydrolysis; Kinetics; Liver - enzymology; Pepsin A; Peptides - chemical synthesis; Rats; Sarcoma, Experimental - enzymology; Structure-Activity Relationship
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)45064-3

The activities of cathepsins D from rat liver and from transplantable rat sarcoma tissue on synthetic peptides were studied. It was shown that, although the two cathepsins are similar in some properties, their binding sites have different structures. Sarcoma cathepsin can split peptides that contain either aromatic or dicarboxylic amino acid residues. Substrates for this enzyme must have peptide chains of at least 5 amino acid residues. Sarcoma cathepsin D displays highest affinity for those substrates that contain dicarboxylic amino acid residues on both sides of the peptide bond cleaved. Replacement of 1 or 2 dicarboxylic amino acid residues by a phenylalanyl residue decreased the apparent affinity of the enzyme for the substrate. Of several structures tested as substrates, the cathepsin D from rat liver has been observed to split only those peptides that contain an aromatic amino acid residue. Both enzymes studied can, like aminopeptidase, split off the NH2-terminal alanyl residue from the peptide Ala-Phe-Gly-Leu-Asp-Val. The synthetic substrate for pepsin, acetyl-Phe-Tyr, inhibits competitively rat liver cathepsin but has no effect on sarcoma cathepsin.