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101.
DNA-binding of water-soluble furocoumarins: a thermodynamic and conformational approach to understanding different biological effects.
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The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix. From the dependence of the binding on ionic strength, ion release and binding free energy corrected for counterion release have been quantitatively estimated. It is shown that the differences in DNA-affinity observed for compounds I and II arise primarily from non electrostatic contributions. The binding process is exothermic, with slightly different van't Hoff enthalpies for the examined furocoumarins. Helix lengthening and dichroic effects indicate different intercalation geometries for the isomeric compounds. These studies allow a possible explanation for the finding that isomer I exhibits largely better DNA-photobinding properties, while isomer II is by far more effective as an antiviral agent. 相似文献
102.
Oriana Tabarrini Claudia Sissi Arnaldo Fravolini Manlio Palumbo 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1327-1336
Abstract A new 6-desfluoroquinolone derivative, characterized by the presence of a 6-hydroxyl group instead of the usual fluorine atom at the C-6 position, was synthesized with the aim to better understand the mechanistic role of the C-6 substituent in the quinolone/DNA/DNA-gyrase interaction. The antibacterial activity unambiguously shows that the hydroxyl group is a good substitute for the C-6 fluorine atom, especially against Gram-positive bacteria. On the contrary, it is a very weak inhibitor of the target DNA gyrase, displaying the highest IC50 value observed for all the C-6 substituted analogues. This behaviour could be explained on the basis of its DNA binding properties. 相似文献
103.
Barbara Gatto Giuseppe Zagotto Claudia Sissi Manlio Palumbo 《International journal of biological macromolecules》1997,21(4):319-326
The quest for more specific drugs in antitumor chemotherapy led us to the design of anthraquinone–peptide conjugates capable of selective recognition of the nucleic acid. We present here the DNA binding characteristics, sequence specificity and geometry of interaction of a pair of enantiomers containing the lysine–glycine dipeptide in the side chains. The d enantiomer binds right handed double stranded DNA more efficiently than the l form under all conditions tested. The source of higher binding affinity is not electrostatic in nature and rests in the more favorable hydrophobic contacts of the d-lysyl side chains in the drug-DNA complex. Both derivatives exhibit preference for alternating GC base sequences and intercalate into DNA in a threading mode as suggested by chiroptical and theoretical studies. The d enantiomer, being a peptidyl derivative that contains a non-natural amino acid, has the considerable advantage of being less susceptible to enzymatic hydrolysis and could therefore represent a lead compound for further development. 相似文献
104.
Giuseppe. Zagotto Giovanni. Mitaritonna Claudia. Sissi Manlio. Palumbo 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):2135-2141
Abstract Aminoacyl-hydroxy-anthraquinones bearing glicyl, varyl, lysyl and tryptophanyl residues in the side-chain were synthesized as new potential DNA-directed drugs. These compounds bind very tightly to double-stranded DNA by intercalating their planar portion into the nucleic acid and further stabilizing the complex through electrostatic contacts with the backbone phosphates. All protonated groups in the side-chains participate in the latter process. The free energy of DNA-binding corrected for the electrostatic contribution is similar for the lysyl and glicyl derivatives, which points to a common geometry of intercalation. 相似文献
105.
106.
Replication dynamics at common fragile site FRA6E 总被引:4,自引:0,他引:4
Elisa Palumbo Laura Matricardi Elena Tosoni Aaron Bensimon Antonella Russo 《Chromosoma》2010,119(6):575-587
The replication dynamics at common fragile site FRA6E has been evaluated by molecular combing and interphase fluorescent in situ hybridisation (FISH) in primary human lymphocytes
cultured under normal or aphidicolin-induced stress conditions. FRA6E is one of the most frequently expressed common fragile sites of the human genome. It harbours several genes, PARK2 being regarded as the most relevant one. According to the results obtained from interphase FISH analysis, FRA6E can be considered a mid-late-replicating sequence characterised by heterogeneous replication timing. Molecular combing did
not reveal specific replication parameters at the fragile site: fork rates were highly comparable to those detected at an
early replicating locus (LMNB2) used as control and in very good agreement with the whole-genome data obtained in parallel. The same indication applied
to the density of initiation zones, the inter-origin distances from adjacent ongoing forks, the frequencies of unidirectional
forks, fork arrest events and asynchronous forks. Interestingly, PARK2 appeared embedded in an early/late replication transition zone, corresponding to intron 8 (162 kb) and to the fragility core
of FRA6E. In cells exposed to aphidicolin, few forks progressing at a rather slow rate were observed, the majority of them being unidirectional,
but again a specific response of the fragile site was not observed. In summary, at FRA6E the replication process is not impaired per se, but chromosome breakages occur preferentially at an early/late replication
transition zone. Aphidicolin might increase the occurrence of breakage events at FRA6E by prolonging the time interval separating the replication of early and late replication domains. These results may be of
general significance to address the problem of fragile site instability. 相似文献
107.
B Di Jeso S Formisano G Palumbo 《Biochemical and biophysical research communications》1985,127(1):37-43
The present investigation demonstrates that the cross-linking agent, dimethylsuberimidate, is an usefull tool to study thyroglobulin structure. In fact, while reproducible and discrete polymerization products are obtained in strictly controlled conditions, valuable information on the native assemblage of thyroglobulin subunits and the effects of its major post-translational modification (iodination) on its structure, are reported. 相似文献
108.
109.
Dr. Carla Palumbo 《Cell and tissue research》1986,246(1):125-131
Summary Morphology and ultrastructure of osteoid-osteocytes were studied in serial thin sections (700–800 Å thick) of periosteal woven bone in tibiae of 15-day-old chick embryos. The three-dimensional shapes of 21 partially, and of one fully sectioned cell were reconstructed manually and by means of a computer-assisted image analyser.Osteoid-osteocytes are active cells engaged in organic matrix secretion and calcification. Like osteoblasts, their activity seems to be polarized towards the mineralization front, as shown by the presence of cytoplasmic processes on their mineral-facing side and by the position of the nucleus toward the vascular side of the cytoplasm. Cellular processes directed towards blood vessels appear only at a later stage, i.e. when the mineralization starts to spread all round the cell.The asynchrony in formation, together with the observed differences in morphology suggest the hypothesis that the cellular processes of the mineral-facing side are mainly involved in bone formation and those of the vascular side in cell nutrition. 相似文献
110.