15N nuclear magnetic resonance spectroscopy. The nebramycin aminoglycosides.
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Biomedical subjects
Publications and source records attributed to D E Dorman.
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The capsular type-specific antigen of Haemophilus influenzae, type b, has been reported to have a unit structure composed of D-ribose and phosphate. Recently, the presence of ribitol was found in preparations of type b capsular antigen. Our analytical results show equimolar proportions of ribose, ribitol, and phosphate. Periodate oxidation studies, paper chromatography of acidic and alkaline hydrolysates, and NMR spectral data indicate the structure of the capular antigen of H. influenzae b, strain Eagan to be a polyribosylribitol phosphate polymer.
In a continuing effort to study thoroughly the alkaloids of Catharanthus roseus, new dimeric alkaloids were isolated and characterized. Structures are proposed for leurocolombine and vinamidine based on UV, IR, PMR, high-resolution mass spectrometry, and CMR. Pseudovincaleukoblastine diol was identified by PMR and mass spectrometry. Leurocolombine exhibited antimitotic activity and marginal antitumor activity against the Ridgeway osteogenic sarcoma.
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Natural-abundance (13)C nuclear magnetic resonance spectra of ten common nucleotides in neutral, aqueous solutions have been determined and interpreted. The spectra of two of these substances were also determined in acidic solutions, and several of the carbon chemical shifts were found to depend markedly on pH. Within the limited range of concentrations employed, there were observed no carbon chemical-shift changes which could be ascribed to base-stacking or base-pairing phenomena.
The chemical shifts of (13)C in natural abundance have been obtained from nuclear magnetic resonance spectra of scyllo-, myo-, chiro-, and epi-inositols at 15.1 MHz. A set of empirical substitutent parameters were derived and shown to be moderately successful in correlating the (13)C resonance-line positions for these substances. The substituent parameters conform generally to the idea that steric hindrance or porximity effects are of special importance in influencing chemical shifts of carbons in cyclohexane systems.
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Zatosetron is being tested clinically as an antianxiety agent; it is a highly selective antagonist of the serotonin 5-HT3 receptor, with minimal agonist activity. The disposition of [14C]zatosetron was studied in five healthy men after a single oral dose (46.2 mg). Serum levels of radioactivity and parent drug peaked in 3-8 hr. About 15% more radioactivity was measured in red blood cells than in plasma. In serum, the parent compound represented about 85% of the radioactivity, zatosetron-N-oxide represented 10%, and N-desmethyl-zatosetron and 3-hydroxy-zatosetron each represented 2-3%. The t1/2 of zatosetron was 25-37 hr. About 75% of zatosetron added to human plasma became reversibly bound to protein. Concentrations of zatosetron in saliva were generally 10-50% higher than those in serum. About 80% of the administered radioactivity was eliminated in urine and 20% in feces; radioactivity was measurable in the excreta for 10-12 days after drug administration. The major route of metabolism of zatosetron was a stereoselective N-oxidation to form 8-alpha-methyl, 8-beta-oxo zatosetron (zatosetron N-oxide). In urine, approximately 45% of the radioactivity was unchanged zatosetron, 35% was zatosetron N-oxide, 10% was N-desmethyl-zatosetron, and 5% was 3-hydroxy-zatosetron. In feces, 30% of the radioactivity was unchanged zatosetron, and 70% was N-desmethyl-zatosetron. Overall, approximately 60% of the administered zatosetron was metabolized in humans. In a separate multiple-dose study, the disposition of zatosetron was found to be similar to that in the single-dose study.