On March 7, 1989, Kuefner, Ulrike; Lohrmann, Ute; Montejano, Yolanda D.; Vitols, Karin S.; Huennekens, F. M. published an article.Related Products of 53838-27-0 The title of the article was Carboxypeptidase-mediated release of methotrexate from methotrexate α-peptides. And the article contained the following:
Methotrexate (MTX) α-peptides containing representative neutral (alanine), acidic (aspartic acid), and basic (arginine) amino acids were synthesized by a regiospecific route. These peptides were hydrolyzed by carboxypeptidases to yield MTX and the amino acids. Pancreatic carboxypeptidase A (CP-A) hydrolyzed MTX-Ala and, at a much slower rate, MTX-Asp and MTX-Arg. MTX-Ala was also a substrate for pancreatic carboxypeptidase B (CP-B); marginal activity was observed with this enzyme and MTX-Arg. Human serum hydrolyzed only MTX-Arg; biphasic inhibition of this activity by 2-(mercaptomethyl)-3-(guanidinoethyl)thiopropionate was consistent with the known presence of 2 types of endogenous carboxypeptidase (CP-N). Cytotoxicity of the MTX peptides toward L1210 cells in culture was enhanced considerably in the presence of the appropriate carboxypeptidases. MTX-Ala was much less toxic than MTX (ID50 values of 2.0 × 10-6M and 2.4 × 10-8M, resp.), but in the presence of CP-A the ID50 of the peptide improved to 8.5 × 10-8M. Similar results were obtained with MTX-Asp/CP-A and MTX-Ala/CP-B combinations. MTX-Arg showed good cytotoxicity (ID50 of 5.0 × 10-8M), due to CP-N activity in the fetal bovine serum of the culture medium; inclusion of CP-B lowered the ID50 to that of MTX. Possible clin. uses of MTX peptides are discussed. The experimental process involved the reaction of (S)-5-tert-Butyl 1-methyl 2-aminopentanedioate(cas: 53838-27-0).Related Products of 53838-27-0
The Article related to methotrexate peptide preparation cytotoxicity carboxypeptidase, antitumor methotrexate peptide prodrug preparation, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Related Products of 53838-27-0
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