排序方式: 共有170条查询结果,搜索用时 15 毫秒
81.
Giangreco I Lattanzi G Nicolotti O Catto M Laghezza A Leonetti F Stefanachi A Carotti A 《PloS one》2011,6(10):e25597
Matrix metalloproteinases (MMP) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A) in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S(1)' specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S(1)' subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC(50) = 7.06) is found for BAM, a compound exhibiting also selectivity (>20) towards MMP-2, as compared to MMP-9, the other member of the gelatinases. 相似文献
82.
Ferino G González-Díaz H Delogu G Podda G Uriarte E 《Biochemical and biophysical research communications》2008,372(2):320-325
In prostate cancer (PCa), prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic, and biomolecular levels. Blood contains a treasure of previously unstudied biomarkers that could reflect the ongoing physiological state of all tissue. The serum prostate-specific antigen (PSA) measurement is a very good biomarker for PCa, but the percentage of bad classification is somewhat high. The blood proteome mass spectra (MS) represent a potential tool for detection of diseases; however the identification of a single biomarker from the complex output from MS is often difficult. In this paper, we propose a general strategy, based on computational chemistry techniques, which should improve the predictive power of PSA. Our group adapted the square-spiral graph to represent human serum-plasma-proteome MS for healthy and PCa patients. These graphs were previously applied to DNA and/or protein sequences. In this work, we calculated different classes of connectivity indices (CIs), and created various models based on the spectral moments. The best QPDRs model found showed accuracy values ranging from 71.7% to 97.2%, and 70.4% to 99.2% of specificity. This methodology might be useful for several applications in computational chemistry. 相似文献
83.
Sandra Gemma Luisa Savini Maria Altarelli Pierangela Tripaldi Luisa Chiasserini Salvatore Sanna Coccone Vinod Kumar Caterina Camodeca Giuseppe Campiani Ettore Novellino Sandra Clarizio Giovanni Delogu Stefania Butini 《Bioorganic & medicinal chemistry》2009,17(16):6063-6072
A series of 4-quinolylhydrazones was synthesized and tested in vitro against Mycobacterium tuberculosis. At a concentration of 6.25 μg/mL, most of the newly synthesized compounds displayed 100% inhibitory activity against M. tuberculosis in cellular assays. Further screening allowed the identification of very potent antitubercular agents. Compound 4c was also tested in a time-course experiment and against mtb clinical isolates, displaying interesting results. 相似文献
84.
Giulia Maurizi Antonella Poloni Domenico Mattiucci Spartaco Santi Angela Maurizi Valerio Izzi Angelica Giuliani Stefania Mancini Maria Cristina Zingaretti Jessica Perugini Ilenia Severi Massimo Falconi Marco Vivarelli Maria Rita Rippo Silvia Corvera Antonio Giordano Pietro Leoni Saverio Cinti 《Journal of cellular physiology》2017,232(10):i-i
85.
Maria?Giovanna?Vilia Marta?Tocchetti Eleonora?Fonte Ilenia?Sana Marta?MuzioEmail author 《European cytokine network》2017,28(2):63-69
IL-1R8, also known as SIGIRR or TIR8, is a trans-membrane protein belonging to the IL-1 receptor family. The human gene includes ten exons, and alternative splicing can result in different isoforms. We, herein, characterized a longer isoform of IL-1R8 containing an in-frame additional sequence between the TIR domain and the C-terminal portion of the protein. IL-1R8 Long (IL-1R8L1) mRNA was specifically expressed and regulated in distinct cell lines, in a manner similar to the classic isoform. Overexpression of IL-1R8L1 resulted in the production of a corresponding protein that showed a pattern of cell localization similar to the classic isoform. An antibody directed against an IL-1R8L1 specific peptide, detected this novel isoform in different cell lines and tissues where this protein may complement the anti-inflammatory functions of classic IL-1R8. 相似文献
86.
Zanetti S Faedda R Fadda G Dupré I Molicotti P Ortu S Delogu G Sanguinetti M Ardito F Sechi LA 《The new microbiologica》2001,24(2):189-192
Mycobacterium neoaurum is a novel species of Mycobacteria, until now only isolated from catheters in immunosuppressed patients. This report describes the isolation and identification of M. neoaurum from urine obtained from a hospitalized patient. 相似文献
87.
Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin 总被引:4,自引:0,他引:4
Temmerman S Pethe K Parra M Alonso S Rouanet C Pickett T Drowart A Debrie AS Delogu G Menozzi FD Sergheraert C Brennan MJ Mascart F Locht C 《Nature medicine》2004,10(9):935-941
Although post-translational modifications of protein antigens may be important componenets of some B cell epitopes, the determinants of T cell immunity are generally nonmodified peptides. Here we show that methylation of the Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA) by the bacterium is essential for effective T cell immunity to this antigen in infected healthy humans and in mice. Methylated HBHA provides high levels of protection against M. tuberculosis challenge in mice, whereas nonmethylated HBHA does not. Protective immunity induced by methylated HBHA is comparable to that afforded by vaccination with bacille Calmette et Guérin, the only available anti-tuberculosis vaccine. Thus, post-translational modifications of proteins may be crucial for their ability to induce protective T cell-mediated immunity against infectious diseases such as tuberculosis. 相似文献
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89.
Gravante G Delogu D Esposito G Montone A 《Plastic and reconstructive surgery》2007,120(1):362; author reply 362-362; author reply 363
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