Protein binding of N-2-mercaptoethyl-1,3-diaminopropane via mixed disulfide formation after oral administration of WR 2721
Earlier studies have shown that WR 2721 (H2N-(CH2)3-NH(CH2)2SPO3H2) is converted to its free thiol form, N-2-mercaptoethyl-1,3-diaminopropane (MDP), at the acidic pH of the stomach. MDP is a radioprotective compound and a mucolytic agent capable of decreasing sputum viscosity in the lungs of patients with cystic fibrosis. Conversion of WR 2721 and MDP to the corresponding sulfonic acid (MDP-SO3H) permits quantitative determination of these compounds in physiological fluids by use of an automatic amino acid analyzer. After oral administration of WR 2721 to human patients and rabbits it is converted to MDP and the free thiol form of the drug associates with plasma proteins by mixed disulfide linkage. The plasma proteins serve as a depot and reservoir of MDP for potential exchange at the tissues. When incubated with whole sputum or with purified mucin solutions in vitro, MDP decreased the viscosity of these solutions by reduction of the accessible disulfide bonds of the mucin molecule and was subsequently found in mixed disulfide association with the mucin molecule. The association of MDP with proteins via mixed disulfide linkage has important implications for the development of optimal dose regimens for administration of WR 2721 to patients.
- Research Organization:
- The Rockefeller University, New York, New York
- OSTI ID:
- 5463243
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 220:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
MERCAPTOPROPYLAMINE
BONDING
METABOLISM
PROTEINS
RADIOPROTECTIVE SUBSTANCES
QUANTITATIVE CHEMICAL ANALYSIS
BLOOD PLASMA
ORAL ADMINISTRATION
PATIENTS
RABBITS
SALIVA
SULFONIC ACIDS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
CHEMICAL ANALYSIS
DRUGS
FABRICATION
JOINING
MAMMALS
MATERIALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
VERTEBRATES
560151* - Radiation Effects on Animals- Man
560152 - Radiation Effects on Animals- Animals
400102 - Chemical & Spectral Procedures