NAcSDKP Analogues Resistant to Angiotensin-Converting Enzyme

• Published in: Journal of medicinal chemistry Vol. 40; no. 24; pp. 3963 - 3968
• Main Authors: Gaudron, Sandrine, Adeline, Marie-Thérèse, Potier, Pierre, Thierry, Josiane
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.11.1997; Amer Chemical Soc
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Chemistry, Medicinal; Chromatography, High Pressure Liquid; Drug Stability; General aspects; Growth Inhibitors - chemistry; Growth Inhibitors - metabolism; Hydrolysis; Kinetics; Life Sciences & Biomedicine; Medical sciences; Oligopeptides - chemistry; Oligopeptides - metabolism; Oligosaccharides - chemistry; Oligosaccharides - metabolism; Peptidyl-Dipeptidase A - metabolism; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Rabbits; Science & Technology; Structure-Activity Relationship; PLASMA; PSEUDOPEPTIDE ANALOGS; BIOLOGICAL-ACTIVITIES; DEGRADATION; AGENTS; INHIBITORS; PEPTIDE; Antineoplastic agent; Peptides; Toxicity; Stem cell; Lung; Hematopoietic cell; Rabbit; Prevention; Structure activity relation; Tetrapeptide; Hematopoiesis; Peptidyl-dipeptidase A; Chemical synthesis; Enzyme; Lagomorpha; In vitro; Peptidases; Hydrolysis resistance; Vertebrata; Chemotherapy; Chemical modification; Mammalia; Animal; Hydrolases; Peptidyl-dipeptidases
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm9701132

Two series of analogues of the tetrapeptide NAcSDKP, an inhibitor of hematopoietic stem cell proliferation, were prepared, and their enzymatic stability toward rabbit lung angiotensin-converting enzyme (ACE) was evaluated as well as their capacity to inhibit NAcSDKP hydrolysis by this enzyme. In the first series, each of the peptide bonds has been successively replaced by an aminomethylene bond. In the second one, the C-terminus of the peptide has been modified by decarboxylation or amidation. The results reported here indicate that all of these molecules but one have good stability toward the enzyme but none of the compounds is able to inhibit NAcSDKP hydrolysis by ACE.