Biomedical subjects

C Fenselau

Publications and source records attributed to C Fenselau.

148 records · Page 9Linked to original sources

PubMedDate not supplied

Iminocyclophosphamide as a chemically reactive metabolite of cyclophosphamide.

Iminocyclophosphamide has been identified among the metabolites produced by incubation of cyclophosphamide with cytochrome P-450 mono-oxygenase immobilized on beaded Sepharose. The reactive imine was trapped by addition of hydrogen cyanide, and the product, 4-cyanocyclophosphamide, was identified by comparison of its chromatographic and mass-spectral properties with those of a synthetic standard. Iminocyclophosphamide was also generated chemically from 4-hydroperoxycyclophosphamide and characterized both by addition of hydrogen cyanide and by reduction with sodium borodeuteride. The synthesis of authentic 4-cyanocyclophosphamide is also reported.

Animals↗

PubMedDate not supplied

Synthesis and analysis of glucuronides of N-hydroxyamides.

Reactions of five N-hydroxyacetylarylamines (N-hydroxyphenacetin, N-hydroxyacetanilide, N-hydroxy-p-chloroacetanilide, N-hydroxy-2-acetylaminonaphthalene, and N-hydroxy-2-acetylaminofluorene) with uridine 5'-diphosphoglucuronic acid catalyzed by immobilized glucuronyl transferase enzyme resulted in the formation of glucuronides conjugated at the N-hydroxyl group. Chromatographic properties of these compounds were examined by using thin layer, gas liquid, and high pressure liquid chromatography. A variety of mass spectrometric techniques were also evaluated for characterization of compounds of this class, including fast atom bombardment, chemical ionization, and electron impact. Electron impact spectra of the trimethylsilyl derivatives contain class characteristic ions and fragmentation pathways that would permit the special nature of the site of conjugation of this important class of compounds to be recognized in glucuronides of undetermined structure. Molecular ion species were not reliably detected in the electron impact spectra; however, these were readily distinguishable by the other two techniques.

Amides↗

PubMedDate not supplied

Quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine.

The quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine were shown to be conjugated in vitro using an immobilized rabbit hepatic microsomal enzyme preparation. It was shown that fast atom bombardment mass spectrometry could be used for direct characterization of these involatile, thermally labile metabolites. The quaternary ammonium-linked glucuronides of amitriptyline and imipramine were demonstrated to be present in urine from patients receiving therapeutic doses of these tricyclic antidepressants.

Amitriptyline↗

PubMedDate not supplied

A strategy for characterization of polyethylene glycol-derivatized proteins. A mass spectrometric analysis of the attachment sites in polyethylene glycol-derivatized superoxide dismutase.

Base treatment of polyethylene glycol-derivatized superoxide dismutase in which the polyethylene glycol is linked to the protein via a succinyl bridge, removes the polyethylene glycol leaving a succinyl marker. Exhaustive succinylation with d4-succinic anhydride completes the derivatization in order to minimize fractionation in proteolysis, chromatography, and desorption in the mass spectrometer. Production of peptides from the derivatized protein for high resolution and high-resolution tandem MS allows identification of the site that had been derivatized by polyethylene glycol and the determination of the amount of polyethylene glycol originally at each site. The mass spectrometric strategy outlined herein can be applied to other proteins derivatized for therapeutic administration.

Amino Acid Sequence↗