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991.
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Mammalian iron homeostasis must be meticulously regulated so that this essential element is available for use, but at the same time prevented from promoting the formation of toxic radicals. Controlling the entry of iron into blood plasma is the main mechanism by which iron stores in the body are physiologically manipulated and regulated. Defects in iron acquisition at the cellular and systemic levels lead to human disorders, which involve either iron overload or iron deficiency. Discoveries of iron transporters and insights into their regulation have provided important information about iron metabolism and genetic iron disorders. 相似文献
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Pompilio A Piccolomini R Picciani C D'Antonio D Savini V Di Bonaventura G 《FEMS microbiology letters》2008,287(1):41-47
We tested 40 clinical Stenotrophomonas maltophilia strains to investigate the possible correlation between adherence to and formation of biofilm on polystyrene, and cell surface properties such as hydrophobicity and motility. Most of the strains were able to adhere and form biofilm, although striking differences were observed. Eleven (27.5%) of the strains were hydrophobic, with hydrophobicity greatly increasing as S. maltophilia attached to the substratum. A positive correlation was observed between hydrophobicity and levels of both adhesion and biofilm formation. Most of the isolates showed swimming and twitching motility. A highly significant negative correlation was observed between swimming motility and level of hydrophobicity. Hydrophobicity is thus a significant determinant of adhesion and biofilm formation on polystyrene surfaces in S. maltophilia. 相似文献
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Camarda V Trapella C Calo' G Guerrini R Rizzi A Ruzza C Fiorini S Marzola E Reinscheid RK Regoli D Salvadori S 《Bioorganic & medicinal chemistry》2008,16(19):8841-8845
Neuropeptide S (NPS) has been identified as the endogenous ligand of a previously orphan receptor now named NPSR. Previous studies demonstrated that the N-terminal sequence Phe(2)-Arg(3)-Asn(4) of the peptide is crucial for biological activity. Here, we report on a focused structure-activity study of Arg(3) and Asn(4) that have been replaced with a series of coded and non-coded amino acids. Thirty-eight human NPS analogues were synthesized and pharmacologically tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPSR. The results of this study demonstrated the following NPS position 3 structure-activity features: (i) the guanidine moiety and its basic character are not crucial requirements, (ii) an aliphatic amino acid with a linear three carbon atom long side chain is sufficient to bind and fully activate NPSR, (iii) the receptor pocket allocating the position 3 side chain can accommodate slightly larger side chains at least to a certain degree [hArg, Arg(NO2) or Arg(Me)2 but not Arg(Tos)]. Position 4 seems to be more sensitive to amino acids replacement compared to position 3; in fact, all the amino acid replacements investigated produced either an important decrease of biological activity or generated inactive derivatives suggesting a pivotal role of the Asn(4) side chain for NPS bioactivity. 相似文献
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Francesco?P.?Intini Angelina?Boccarelli Valentina?C.?Francia Concetta?Pacifico Maria?F.?Sivo Giovanni?Natile Domenico?Giordano Pietro?De?Rinaldis Mauro?ColucciaEmail author 《Journal of biological inorganic chemistry》2004,9(6):768-780
Both trans- and cis-[PtCl2(NH3)(L)] compounds have been synthesized, L representing either the imino ether HN=C(OMe)Me having a Z or E configuration at the C=N double bond, or the cyclic ligands
and
(compounds 1–4 for trans geometry and 5–8 for cis geometry, respectively). The cyclic ligands mimic the imino ether ligands but, differently from imino ethers, cannot undergo change of configuration. In a panel of human tumor cells, trans compounds inhibit growth much more than transplatin. Moreover, compound 1 in most cases is less active than 2, and 1 and 2 are less active than 3 and 4, respectively. For cis compounds with imino ethers, the activity is reduced (5) or unaffected (6) with respect to cisplatin. Moreover, unlike trans compounds, substitution of cyclic ligands (7, 8) for imino ethers (5, 6) generally decreases the activity. This determines, for compounds with cyclic ligands, an unusual inversion of the cis geometry requirement for activity of platinum(II) species. Importantly, 1–4 and 5–8 partially circumvent the multifocal cisplatin resistance of A2780cisR cells, and 1–4 also overcome resistance from reduced uptake of 41McisR cells. DNA interaction regioselectivity of 1–4 and 5–8 is not substantially modified with respect to transplatin and cisplatin. However, both imino ethers and cyclic ligands slow down the DNA interstrand cross-link reaction, (E)-HN=C(OMe)Me and
decreasing also its extent. Therefore, DNA interaction of 1–4 and 5–8 appears to be characterized by persistent monoadducts (1–4), and by monoadducts and/or intrastrand cross-links structurally different from those of cisplatin (5–8). This study demonstrates that ligand configuration modulates the activity of both trans and cis compounds, and supports the development of platinum drugs based on their coordination chemistry to combat cisplatin resistance.F.P. Intini and A. Boccarelli contributed equally to this work 相似文献