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Christian Tessier Gian-Paolo Rossini Jean-François Pageaux Hélène Cohen Michel Lagarde Christian Laugier Jean-Michel Fayard 《FEBS letters》1996,390(3):311-314
Rat uterine stromal cells (UIII) express pancreatic type PLA2 (PLA2-I) receptor and internalize the enzyme bound to receptors. Here, we investigate the proliferating effect and alterations in binding of PLA2-I. There is a dramatic decline in PLA2-I binding in UIII cells as they progress from a nonconfluent proliferating state (40,000 sites/cell) to a confluent state (1300 sites/cell). Intracellular concentration of PLA2-I changed with the alteration in binding, suggesting that regulation in the PLA2 binding capacity may have important implications in growth control mechanisms. 相似文献
2.
Flavio Curnis Angela Cattaneo Renato Longhi Angelina Sacchi Anna Maria Gasparri Fabio Pastorino Paola Di Matteo Catia Traversari Angela Bachi Mirco Ponzoni Gian-Paolo Rizzardi Angelo Corti 《The Journal of biological chemistry》2010,285(12):9114-9123
Various NGR-containing peptides have been exploited for targeted delivery of drugs to CD13-positive tumor neovasculature. Recent studies have shown that compounds containing this motif can rapidly deamidate and generate isoaspartate-glycine-arginine (isoDGR), a ligand of αvβ3-integrin that can be also exploited for drug delivery to tumors. We have investigated the role of NGR and isoDGR peptide scaffolds on their biochemical and biological properties. Peptides containing the cyclic CNGRC sequence could bind CD13-positive endothelial cells more efficiently than those containing linear GNGRG. Peptide degradation studies showed that cyclic peptides mostly undergo NGR-to-isoDGR transition and CD13/integrin switching, whereas linear peptides mainly undergo degradation reactions involving the α-amino group, which generate non-functional six/seven-membered ring compounds, unable to bind αvβ3, and small amount of isoDGR. Structure-activity studies showed that cyclic isoDGR could bind αvβ3 with an affinity >100-fold higher than that of linear isoDGR and inhibited endothelial cell adhesion and tumor growth more efficiently. Cyclic isoDGR could also bind other integrins (αvβ5, αvβ6, αvβ8, and α5β1), although with 10–100-fold lower affinity. Peptide linearization caused loss of affinity for all integrins and loss of specificity, whereas α-amino group acetylation increased the affinity for all tested integrins, but caused loss of specificity. These results highlight the critical role of molecular scaffold on the biological properties of NGR/isoDGR peptides. These findings may have important implications for the design and development of anticancer drugs or tumor neovasculature-imaging compounds, and for the potential function of different NGR/isoDGR sites in natural proteins. 相似文献
3.
Spitaleri A Mari S Curnis F Traversari C Longhi R Bordignon C Corti A Rizzardi GP Musco G 《The Journal of biological chemistry》2008,283(28):19757-19768
Asparagine deamidation at the NGR sequence in the 5th type I repeat of fibronectin (FN-I5) generates isoDGR, an alphavbeta3 integrin-binding motif regulating endothelial cell adhesion and proliferation. By NMR and molecular dynamics studies, we analyzed the structure of CisoDGRC (isoDGR-2C), a cyclic beta-peptide mimicking the FN-I5 site, and compared it with NGR, RGD, or DGR-containing cyclopeptides. Docking experiments show that isoDGR, exploiting an inverted orientation as compared with RGD, favorably interacts with the RGD-binding site of alphavbeta3, both recapitulating canonical RGD-alphavbeta3 contacts and establishing additional polar interactions. Conversely, NGR and DGR motifs lack the fundamental pharmacophoric requirements for high receptor affinity. Therefore, unlike NGR and DGR, isoDGR is a new natural recognition motif of the RGD-binding pocket of alphavbeta3. These findings contribute to explain the different functional properties of FN-I5 before and after deamidation, and provide support for the hypothesis that NGR --> isoDGR transition can work as a molecular timer for activating latent integrin-binding sites in proteins, thus regulating protein function. 相似文献
4.
Ingo Brassat Ulli Englert Wilhelm Keim Dagmar P. Keitel Stefan Killat Gian-Paolo Suranna Ruimin Wang 《Inorganica chimica acta》1998,280(1-2):150-162
A series of cationic nickel complexes [(η3-methally)Ni(PP(O))]SbF6 (1–4) [PP(O) = Ph2P(CH2)P(O)Ph2 (dppmO) (1), Ph2P(CH2)2P(O)Ph2 (dppeO) (2), Ph2P(CH2)3P(O)Ph2 (dpppO) (3), pTol2P(CH2)P(O)pTol2 (dtolpmO) (4)] has been synthesized in good yields by treatment of [(η3-methally)NiBr]2 with biphosphine monoxides and AgSbF6. The ligands are coordinated in a bidentate way. Starting from [(η3-all)PdI]2 the cationic complexes [(η3-all)PP(O))]Y (8–14). [PP(O) = dppmO, dppeO, dpppO, dtolpmO;Y = BF4, SbF6, CF3SO3, pTolSO3] were synthesized in good yields. The coordination mode of the ligand is dependent on the backbone and the anion, revealing a monodentate coordination with dppmO for stronger coordinating anions. The intermediates [(η3-all)Pd(I)(PP(O)-κ1-P)] (5–7) [PP(O) = dppmO (5), dppeO (6), dtolpmO (7)] were isolated and characterized. Neutral methyl complexes [(Cl)(Me)Pd(PP(O))] (15–18). [PP(O) = dppmO (15), dppeO (16), dpppO (17), dtolpmO (18)] can easily be obtained in high yields starting from [(cod)PdCl2]. For dppmO two different routes are presented. The structure of [(Me)(Cl)Pd{;Ph2P(CH2-P(O)Ph2-κ2-P,O};] · CH2Cl2 (15) with the chlorine atom trans to phosphorus was determined by X-ray diffraction. 相似文献
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Evidence for a direct link between glutathione biosynthesis and stress defense gene expression in Arabidopsis 总被引:20,自引:0,他引:20 下载免费PDF全文
Ball L Accotto GP Bechtold U Creissen G Funck D Jimenez A Kular B Leyland N Mejia-Carranza J Reynolds H Karpinski S Mullineaux PM 《The Plant cell》2004,16(9):2448-2462
The mutant regulator of APX2 1-1 (rax1-1) was identified in Arabidopsis thaliana that constitutively expressed normally photooxidative stress-inducible ASCORBATE PEROXIDASE2 (APX2) and had >/=50% lowered foliar glutathione levels. Mapping revealed that rax1-1 is an allele of gamma-GLUTAMYLCYSTEINE SYNTHETASE 1 (GSH1), which encodes chloroplastic gamma-glutamylcysteine synthetase, the controlling step of glutathione biosynthesis. By comparison of rax1-1 with the GSH1 mutant cadmium hypersensitive 2, the expression of 32 stress-responsive genes was shown to be responsive to changed glutathione metabolism. Under photo-oxidative stress conditions, the expression of a wider set of defense-related genes was altered in the mutants. In wild-type plants, glutathione metabolism may play a key role in determining the degree of expression of defense genes controlled by several signaling pathways both before and during stress. This control may reflect the physiological state of the plant at the time of the onset of an environmental challenge and suggests that changes in glutathione metabolism may be one means of integrating the function of several signaling pathways. 相似文献
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Qiong Wang Edoardo Mosconi Christian Wolff Junming Li Dieter Neher Filippo De Angelis Gian Paolo Suranna Roberto Grisorio Antonio Abate 《Liver Transplantation》2019,9(28)
Two new hole selective materials (HSMs) based on dangling methylsulfanyl groups connected to the C‐9 position of the fluorene core are synthesized and applied in perovskite solar cells. Being structurally similar to a half of Spiro‐OMeTAD molecule, these HSMs (referred as FS and DFS) share similar redox potentials but are endowed with slightly higher hole mobility, due to the planarity and large extension of their structure. Competitive power conversion efficiency (up to 18.6%) is achieved by using the new HSMs in suitable perovskite solar cells. Time‐resolved photoluminescence decay measurements and electrochemical impedance spectroscopy show more efficient charge extraction at the HSM/perovskite interface with respect to Spiro‐OMeTAD, which is reflected in higher photocurrents exhibited by DFS/FS‐integrated perovskite solar cells. Density functional theory simulations reveal that the interactions of methylammonium with methylsulfanyl groups in DFS/FS strengthen their electrostatic attraction with the perovskite surface, providing an additional path for hole extraction compared to the sole presence of methoxy groups in Spiro‐OMeTAD. Importantly, the low‐cost synthesis of FS makes it significantly attractive for the future commercialization of perovskite solar cells. 相似文献
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Ciccarella G Spadavecchia J Rella R Vasapollo G Mastrorilli P Suranna GP 《Biosensors & bioelectronics》2006,22(3):415-422
Spin-coated films of 29H,31H-tetra-4-(2,4-di-tert-amylphenoxy)phthalocyanine (H(2)Pc) and [kappaP,mu-kappaS-(dppeS)Pt(CH(3))](2)[BF(4)](2) have been used as sensing layers deposited in thin film form for the detection of VOCs. The sensing behaviour of the blend was predicted on the basis of mass spectrometric determinations performed on H(2)Pc/Pt-complex solutions, by monitoring the formation of gas-phase ions at the electrospray interface. The addition of small amounts of acetonitrile produced a [M+41](+) peak whereas the addition of similar amounts of methanol, ethanol and isopropyl alcohol did not give the corresponding [M+ROH](+) species. These results were confirmed by sensing tests. A pure phthalocyanine optosensing element did not show relevant selectivity. Conversely, the heterogeneous sensing layer obtained by spin-coating deposition of a Pt-complex/H(2)Pc blend allowed the sensing of acetonitrile vapours with respect to the above mentioned alcohols. 相似文献
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Paola Di Matteo Gian Luigi Arrigoni Luca Alberici Angelo Corti Corrado Gallo-Stampino Catia Traversari Claudio Doglioni Gian-Paolo Rizzardi 《The journal of histochemistry and cytochemistry》2011,59(1):47-59
Aminopeptidase-N (CD13) is an important target of tumor vasculature-targeting drugs. The authors investigated its expression by immunohistochemistry with three anti-CD13 monoclonal antibodies (WM15, 3D8, and BF10) in normal and pathological human tissues, including 58 normal, 32 inflammatory, and 149 tumor tissue specimens. The three antibodies stained vessels in most neoplastic tissues, interestingly with different patterns. As a matter of fact, WM15 stained almost all intratumor and peritumor capillaries and only partially large vessels, whereas BF10 and 3D8 reacted with arteries and venules and to a lesser extent with capillaries. These antibodies also stained the stroma in about half of neoplastic tissues. In inflammatory lesions, the three antibodies stained vessels and stroma, whereas in normal tissues, they stained a small percentage of blood vessels. Finally, the three antibodies failed to stain endothelial cells of normal colon, whereas they reacted with activated human umbilical vein endothelial cells and with endothelial cells of colon adenocarcinoma vessels. Overall, WM15 was the most specific antibody for angiogenic tumor vessels, suggesting that it may be a good tool for detecting the CD13 form associated with the tumor vasculature. This finding may be relevant for CD13-mediated vascular targeting therapies. 相似文献
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As a result of the spread of TYLCV on tomato crops, reliable and rapid diagnostic tools to identify and isolate new sources
of infection are necessary. We tested several methods, based both on antibodies and on nonradioactive DNA probes. Indirect
plate-trapping ELISA was only effective in detecting the virus in purified preparations, but not in crude extracts. Dot-ELISA
with chemiluminescence detection gave satisfactory results when young stems were directly squashed on membranes. A digoxigenin-labeled
probe, detected with chemiluminescence, was used in leaf squashes and dot blots. Best results were obtained with dot blots
of total nucleic acids prepared with a fast and safe procedure. TYLCV DNA was readily and reliably detected in spots corresponding
to 15 μg fresh weight. When weak signals were observed, total extracts were analyzed by Southern blotting, to confirm the
presence of viral DNA forms. 相似文献
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