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M E Rosen

Publications and source records attributed to M E Rosen.

4 recordsLinked to original sources

NMR studies of the paramagnetic complex Fe(II)-bleomycin.

The coordination chemistry of the iron(II) complex of the antitumor drug bleomycin has been extensively investigated with a number of spectroscopic and chemical techniques. However, the actual structure of this complex is not established. In this report, we present NMR studies of the paramagnetic Fe(II)BLM and use one- and two-dimensional methods to assign the paramagnetically shifted features to particular protons. The data analysis points toward the primary and secondary amines of the beta-aminoalanine fragment, the pyrimidine and imidazole rings, and the amide nitrogen of the beta-hydroxyhistidine fragment as ligands to the metal center. Correlation of the T1 values with the metal-proton distances derived from the NMR-generated solution structure of HOO-Co(III)BLM [Wu, W., Vanderwall, D. E., Lui, S. M., Tang, X.-J., Turner, C. J., Kozarich, J. W., & Stubbe, J. (1996) J. Am. Chem. Soc. 118, 1268-1280] indicates that the two metallobleomycins share similar structures. The chemical shifts as well as the T1 values of the sugar protons indicate that these fragments are close but not bound to the metal in Fe(II)BLM.

Antineoplastic Agents↗

Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. II. Glucoprivation.

Estrous cycles in Syrian hamsters are inhibited by food deprivation or treatment with pharmacological inhibitors of intracellular glucose utilization (glucoprivic treatments). These same metabolic challenges increase neural stimulation in areas of the caudal brain stem thought to be involved in detection of metabolic signals. Experiment 1 was designed to examine whether vagally transmitted signals are important for glucoprivic effects on estrous cycles and on neural stimulation in the caudal brain stem. Vagotomized or sham-operated hamsters were treated with 2-deoxy-D-glucose (2-DG) at a dose known to decrease cellular glucose utilization and inhibit estrous cycles (1,750 mg/kg). Vagotomized and sham-operated hamsters did not differ significantly in incidence of 2-DG-induced anestrus or in neural stimulation in the caudal brain stem, but the effects of 2-DG on estrous cycles and neural stimulation appeared to have been attenuated in vagotomized hamsters. In experiment 2, hamsters were injected intracerebroventricularly with 2-DG or glucose at doses that did not induce anestrus when injected systemically (125 and 250 mg/kg). Groups treated with intracerebroventricular injections of 2-DG showed a significantly higher incidence of anestrus than those treated with glucose. In experiment 3, effects of systemic injections of 2-DG were prevented by prior injection of glucose or fructose at the same concentration, indicating that 2-DG acts via effects on glucose metabolism, rather than via a nonspecific pharmacological effect or generalized stress response. Results of these experiments and those reported elsewhere (J. E. Schneider, A. J. Hall, and G. N. Wade. Am. J. Physiol. 272 (Regulatory Integrative Comp. Physiol, 41) R400-R405, 1997] are consistent with the notion that central glucoprivation is sufficient, whereas peripheral lipoprivation is not critical, for metabolic effects on estrous cycles.

Anestrus↗