Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.177 (BIS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Convenient syntheses are described of d4 analogs of cyclophosphamide and some of its metabolites, potential standards for the quantitative analysis of the drug and its metabolites in human body fluids by stable isotope dilution-mass spectrometry. Base-catalyzed H-D exchange on N-nitrosobis(2-hydroxyethyl)amine gave N-nitrosobis(1,1-dideuterio-2-hydroxyethyl)amine from which bis(2-chloro-1,1-dideuterioethyl)amine (nor-HN2-d4) was readily obtained. Established synthetic routes were then used to convert nor-HN2-d4 into d4 analogs of cyclophosphamide [2-[bis(2-chlorethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide], 4-ketocyclophosphamide [2[BIS(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorin-4-one 2-oxide], and carboxyphosphamide [2-carboxyethyl N-N-bis(2-chloroethyl)phosphorodiamidate], and these analogs were used in a preliminary investigation into the quantitation of the appropriate components in human plasma and urine. Also prepared were d4 analogs of phosphoramide mustard [N,N-bis(2-chloroethyl)phosphorodiamidic acid (cyclohexylammonium salt)] and 3-(2-chloroethyl)oxazolidone and the methyl and trideuteriomethyl esters of phosphoramide mustard.
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PMID:Synthesis of deuterium-labeled analogs of cyclophosphamide and its metabolites. 117 55

The selective solute partitioning within a polymeric network is of key importance to applications in which controlled release or uptake of solutes in a responsive hydrogel is required. In this work we investigate the impact of cross-links on solute adsorption in a swollen polymer network by means of all-atom, explicit-water molecular dynamics simulations. We focus on a representative network subunit consisting of poly(N-isopropylacrylamide) (PNIPAM) and N,N'-methylenebisacrylamide (BIS/MBA) cross-linker types. Our studied system consists of one BIS-linker with four atactic PNIPAM chains attached in a tetrahedral geometry. The adsorption of several representative solutes of different polarity in the low concentration limit at the linker region is examined. We subdivide the solute adsorption regions and distinguish between contributions stemming from polymer chains and cross-link parts. In comparison to a single polymer chain, we observe that the adsorption of the solutes to the cross-link region can significantly differ, with details depending on the specific compounds' size and polarity. In particular, for solutes that have already a relatively large affinity to PNIPAM chains the dense cross-link region (where many-body attractions are at play) amplifies the local adsorption by an order of magnitude. We also find that the cross-link region can serve as a seed for the aggregation of mutually attractive solutes at higher solute concentrations. Utilizing the microscopic adsorption coefficients in a mean-field model of an idealized macroscopic polymer network, we extrapolate these results to the global solute partitioning in a swollen hydrogel and predict that these adsorption features may lead to non-monotonic partition ratios as a function of the cross-link density.
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PMID:Cross-linker effect on solute adsorption in swollen thermoresponsive polymer networks. 3085 38