alpha-chymotrypsin and phosphoramide-mustard

alpha-chymotrypsin has been researched along with phosphoramide-mustard* in 1 studies

Other Studies

1 other study(ies) available for alpha-chymotrypsin and phosphoramide-mustard

Article	Year
Phenylalanyl-aminocyclophosphamides as model prodrugs for proteolytic activation: synthesis, stability, and stereochemical requirements for enzymatic cleavage. Bioorganic & medicinal chemistry letters, 2007, Jan-15, Volume: 17, Issue:2 4-Aminocyclophosphamide (4-NH2-CPA, 7) was proposed as a prodrug moiety of phosphoramide mustard. Four diastereomers of phenylalanine-conjugates of 4-NH2-CPA were synthesized and their stereochemistry was assigned based on chromatographic and spectroscopic data. All diastereomers were stable in phosphate buffer but only the cis-(4R)-isomer of 15 was efficiently cleaved by alpha-chymotrypsin with a half-life of 20 min, which is much shorter than the 8.9h to >12h half-lives found for the other diastereomers. LC-MS analysis of the proteolytic products of cis-(4R)-15 indicated that 4-NH2-CPA was released upon proteolysis and further disintegrated to phosphoramide mustard. These results suggest the feasibility of using peptide-conjugated cis-(4R)-4-NH2-CPA as potential prodrugs for proteolytic activation in tumor tissues. Topics: Antineoplastic Agents; Chymotrypsin; Drug Design; Drug Stability; Enzyme Activators; Half-Life; Molecular Conformation; Peptide Hydrolases; Phenylalanine; Phosphoramide Mustards; Prodrugs; Stereoisomerism; Structure-Activity Relationship	2007

Article

Year

Phenylalanyl-aminocyclophosphamides as model prodrugs for proteolytic activation: synthesis, stability, and stereochemical requirements for enzymatic cleavage.

Bioorganic & medicinal chemistry letters, 2007, Jan-15, Volume: 17, Issue:2

4-Aminocyclophosphamide (4-NH2-CPA, 7) was proposed as a prodrug moiety of phosphoramide mustard. Four diastereomers of phenylalanine-conjugates of 4-NH2-CPA were synthesized and their stereochemistry was assigned based on chromatographic and spectroscopic data. All diastereomers were stable in phosphate buffer but only the cis-(4R)-isomer of 15 was efficiently cleaved by alpha-chymotrypsin with a half-life of 20 min, which is much shorter than the 8.9h to >12h half-lives found for the other diastereomers. LC-MS analysis of the proteolytic products of cis-(4R)-15 indicated that 4-NH2-CPA was released upon proteolysis and further disintegrated to phosphoramide mustard. These results suggest the feasibility of using peptide-conjugated cis-(4R)-4-NH2-CPA as potential prodrugs for proteolytic activation in tumor tissues.

Topics: Antineoplastic Agents; Chymotrypsin; Drug Design; Drug Stability; Enzyme Activators; Half-Life; Molecular Conformation; Peptide Hydrolases; Phenylalanine; Phosphoramide Mustards; Prodrugs; Stereoisomerism; Structure-Activity Relationship

2007