Calculations of the optical properties (absorption, linear dichroism, circular dichroism, and ani... more Calculations of the optical properties (absorption, linear dichroism, circular dichroism, and anisotropic components of the CD) are presented for polynucleotides of random or regular sequence within the formalism of the matrix method using a set of parameters that includes only the ππ* transitions of the aromatic bases. Experimental solution spectra agree favorably with calculated CD spectra for A‐RNA, A‐DNA, and B‐DNA, when coordinates derived from x‐ray studies on fibers are used. Excessive hypochromicity is predicted when parameters intended to reproduce the vacuum‐uv absorption of the chromophores are included in the calculations, but total elimination of these parameters leads to an insufficient hypochromicity for the long‐wavelength absorption band. Using alternative conformations for DNA in low‐salt aqueous solution did not improve the agreement between experimental and calculated spectra, but some features of the optical properties predicted for these variant structures sugg...
Intranuclear drug concentration in cells treated with doxorubicin (DXR) or with 4'-deoxy-4... more Intranuclear drug concentration in cells treated with doxorubicin (DXR) or with 4'-deoxy-4'-iododoxorubicin (IDX) was measured by means of a quantitative microspectrofluorometric technique recently developed by us. Resolution of free and bound drug contributions in fluorescence emission spectra, as collected from a microvolume of single living cell nuclei, provided concentration data with about 10% indetermination. Uptake of DXR and IDX into the nucleus of K562 cells and DXR-resistant K562/DXR cells could then be studied with a sensitive, nondestructive technique. Growth inhibitory concentrations of K562 and K562/DXR cells, when measured with respect to drug content in the medium, differed by a factor of 25 in the case of DXR and by a factor of three in the case of IDX. By contrast, intranuclear drug concentrations measured at corresponding growth inhibitory concentrations are found to be nearly constant, i.e., independent of cellular-resistant phenotype and of anthracycline...
Bioorganic & Medicinal Chemistry Letters, 1993
Abstract The molecular event ensuing from β-lactam cleavage of cephem sulfones by chemical nucleo... more Abstract The molecular event ensuing from β-lactam cleavage of cephem sulfones by chemical nucleophiles have been determined. Alkaline hydrolysis and methanolysis led to opening of the dihydrothiazine ring to produce sulfinate salts. Cleavages promoted by ...
Novel pro-apoptotic, homo- and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-li... more Novel pro-apoptotic, homo- and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head-head (8), tail-tail (9) or head-tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8-10 is thoroughly described.
Measurements have been made on the flow dichroism of T7 DNA as a function of NaCl concentration. ... more Measurements have been made on the flow dichroism of T7 DNA as a function of NaCl concentration. In high salt, our results are compatible with an optical factor of −1.4 and a persistence length of 470 Å. The former is in agreement with expectations from the x‐ray diffraction structure of fibrous B–DNA, and the latter is in the midrange of recent determinations. As salt concentration is decreased, the persistence length increases. The relation of our study to other recent investigations and with current theories of the electrostatic contribution to persistence length is discussed. We note that the separation of the electrostatic expansion factor into long‐ and short‐range effects is somewhat arbitrary and might affect the interpretation of different experimental results in different ways. Finally, our hydrodynamic factors are consistent with a chain which is partially free‐draining. This goes against the traditional interpretation but is in agreement with two recent observations.
Calculations of the optical properties (absorption, linear dichroism, circular dichroism, and ani... more Calculations of the optical properties (absorption, linear dichroism, circular dichroism, and anisotropic components of the CD) are presented for polynucleotides of random or regular sequence within the formalism of the matrix method using a set of parameters that includes only the ππ* transitions of the aromatic bases. Experimental solution spectra agree favorably with calculated CD spectra for A‐RNA, A‐DNA, and B‐DNA, when coordinates derived from x‐ray studies on fibers are used. Excessive hypochromicity is predicted when parameters intended to reproduce the vacuum‐uv absorption of the chromophores are included in the calculations, but total elimination of these parameters leads to an insufficient hypochromicity for the long‐wavelength absorption band. Using alternative conformations for DNA in low‐salt aqueous solution did not improve the agreement between experimental and calculated spectra, but some features of the optical properties predicted for these variant structures sugg...
Intranuclear drug concentration in cells treated with doxorubicin (DXR) or with 4'-deoxy-4... more Intranuclear drug concentration in cells treated with doxorubicin (DXR) or with 4'-deoxy-4'-iododoxorubicin (IDX) was measured by means of a quantitative microspectrofluorometric technique recently developed by us. Resolution of free and bound drug contributions in fluorescence emission spectra, as collected from a microvolume of single living cell nuclei, provided concentration data with about 10% indetermination. Uptake of DXR and IDX into the nucleus of K562 cells and DXR-resistant K562/DXR cells could then be studied with a sensitive, nondestructive technique. Growth inhibitory concentrations of K562 and K562/DXR cells, when measured with respect to drug content in the medium, differed by a factor of 25 in the case of DXR and by a factor of three in the case of IDX. By contrast, intranuclear drug concentrations measured at corresponding growth inhibitory concentrations are found to be nearly constant, i.e., independent of cellular-resistant phenotype and of anthracycline...
Bioorganic & Medicinal Chemistry Letters, 1993
Abstract The molecular event ensuing from β-lactam cleavage of cephem sulfones by chemical nucleo... more Abstract The molecular event ensuing from β-lactam cleavage of cephem sulfones by chemical nucleophiles have been determined. Alkaline hydrolysis and methanolysis led to opening of the dihydrothiazine ring to produce sulfinate salts. Cleavages promoted by ...
Novel pro-apoptotic, homo- and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-li... more Novel pro-apoptotic, homo- and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head-head (8), tail-tail (9) or head-tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8-10 is thoroughly described.
Measurements have been made on the flow dichroism of T7 DNA as a function of NaCl concentration. ... more Measurements have been made on the flow dichroism of T7 DNA as a function of NaCl concentration. In high salt, our results are compatible with an optical factor of −1.4 and a persistence length of 470 Å. The former is in agreement with expectations from the x‐ray diffraction structure of fibrous B–DNA, and the latter is in the midrange of recent determinations. As salt concentration is decreased, the persistence length increases. The relation of our study to other recent investigations and with current theories of the electrostatic contribution to persistence length is discussed. We note that the separation of the electrostatic expansion factor into long‐ and short‐range effects is somewhat arbitrary and might affect the interpretation of different experimental results in different ways. Finally, our hydrodynamic factors are consistent with a chain which is partially free‐draining. This goes against the traditional interpretation but is in agreement with two recent observations.
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