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71.
de Champdoré M De Napoli L Di Fabio G Messere A Montesarchio D Piccialli G 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):695-697
An easy and efficient strategy to obtain new nucleoside based solid supports in which the nucleoside moieties have been anchored to the solid support through the nucleobase is here proposed. A simple and efficient solid-phase synthesis of 5' and 3'-derivatized uridine analogues has so been developed, following methodologies well established in organic chemistry. 相似文献
72.
Onori L Aggio A Taddei G Loreto MF Ciccocioppo R Vicini R Tonini M 《American journal of physiology. Gastrointestinal and liver physiology》2003,285(2):G325-G331
In the gastrointestinal tract, tachykinin NK1 receptors are widely distributed in a number of neuronal and nonneuronal cells involved in the control of gut motor activity. In particular, in the rabbit isolated distal colon, which is a suitable model system to investigate the contribution of tachykinins as noncholinergic excitatory transmitters, the influence of NK1 receptors in the regulation of peristalsis is not known. The selective NK1-receptor antagonists SR-140333 (0.3 and 1 nM) and MEN-10930 (0.3-10 nM) significantly enhanced the velocity of rabbit colonic propulsion to submaximal stimulation. The prokinetic effect of SR-140333 was prevented by N(omega)-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, indicating that NK1 receptors located on nitrergic innervation exert a functional inhibitory restraint on the circular muscle and probably on descending excitatory and inhibitory pathways during propulsion. Conversely, the selective NK1-receptor agonist septide (3-10 nM) significantly inhibited colonic propulsion. In the presence of L-NNA, the inhibitory effect of septide was reverted into a prokinetic effect, which is probably mediated by the activation of postjunctional excitatory NK1 receptors. 相似文献
73.
Oliva A Borriello A Zeppetelli S Di Feo A Cortellazzi P Ventriglia V Criscuolo M Zappia V Della Ragione F 《Molecular and cellular biochemistry》2003,247(1-2):55-60
The importance of bone marrow mesenchymal stem cells in hemopoiesis has been definitely demonstrated. Thus, their impairment might cause profound alteration on production and maturation of blood cells. In the present paper, we investigated, for the first time, the effect of retinoic acid, an important antileukemic molecule, on the proliferation of primary cultures of human bone marrow mesenchymal stem cells. We demonstrated that retinoic acid, at a pharmacological concentration, hampers strongly the growth of the cells, without inducing osteoblastic differentiation. The analysis of cell division cycle machinery showed that the antiproliferative effect is associated with (i) the up-regulation of two cyclin-dependent kinase inhibitors, namely p27Kip1 and p16INK4A, and (ii) the down-regulation of cyclin-dependent kinase 2 activity and pRB phosphorylation. The reported findings represent novel insights into the antileukemic effects of the drug and contribute in clarifying the molecular mechanism of its pharmacological activity. 相似文献
74.
Mello GC Oliva ML Sumikawa JT Machado OL Marangoni S Novello JC Macedo ML 《Journal of Protein Chemistry》2001,20(8):625-632
A second trypsin inhibitor (DMTI-II) was purified from the seed of Dimorphandra mollis (Leguminosae-Mimosoideae) by ammonium sulfate precipitation (30–60%), gel filtration, and ion-exchange and affinity chromatography. A molecular weight of 23 kDa was estimated by gel filtration on a Superdex 75 column SDS-PAGE under reduced conditions showed that DMTI-II consisted of a single polypeptide chain, although isoelectric focusing revealed the presence of three isoforms. The dissociation constant of 1.7 × 10–9 M with bovine trypsin indicated a high affinity between the inhibitor and this enzyme. The inhibitory activity was stable over a wide pH range and in the presence of DTT. The N-terminal sequence of DMTI-II showed a high degree of homology with other Kunitz-type inhibitors. 相似文献
75.
DNA replication of phage-plasmid P4 in its host Escherichia coli depends on its replication protein α. In the plasmid state, P4 copy number is controlled by the regulator protein Cnr (copy number regulation). Mutations in α (αcr) that prevent regulation by Cnr cause P4 over-replication and cell death. Using the two-hybrid system in Saccharomyces cerevisiae and a system based on λ immunity in E.coli for in vivo detection of protein–protein interactions, we found that: (i) α protein interacts with Cnr, whereas αcr proteins do not; (ii) both α–α and αcr–αcr interactions occur and the interaction domain is located within the C-terminal of α; (iii) Cnr–Cnr interaction also occurs. Using an in vivo competition assay, we found that Cnr interferes with both α–α and αcr–αcr dimerization. Our data suggest that Cnr and α interact in at least two ways, which may have different functional roles in P4 replication control. 相似文献
76.
Behaviour of interleukin-2 serum levels in advanced non-small-cell lung cancer patients: relationship with response to therapy and survival 总被引:8,自引:0,他引:8
Orditura M Romano C De Vita F Galizia G Lieto E Infusino S De Cataldis G Catalano G 《Cancer immunology, immunotherapy : CII》2000,49(10):530-536
Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses.
In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer
(NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up,
using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response
to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were
shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response
to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate
analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of
IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis.
In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients
with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
Received: 16 March 2000 / Accepted: 27 July 2000 相似文献
77.
Many of the protein precursors traversing the secretory pathway undergo cleavage at multibasic sites to generate their bioactive forms. The proprotein convertases (PCs), a family of subtilisin-like proteases, are the major endoproteases that serve this function. Genes encoding seven distinct members of this family have so far been characterized in vertebrates: furin, PC2, PC1/PC3, PC4, PACE4, PC5/PC6 and PC7/PC8/LPC. Multiple PC genes have also been cloned from a number of invertebrates, including Drosophila melanogaster and Caenorhabditis elegans. These findings suggest that gene duplication and diversification of the PCs have occurred throughout metazoan evolution. To investigate the structural and functional changes which have occurred during vertebrate development, we have analyzed the expression of PC genes in the protochordate amphioxus. We have previously shown that amphioxus express homologous PC2 and PC1/PC3 genes [Proc. Natl. Acad. Sci. USA 92 (1995) 3591]. Here we report the characterization of amphioxus cDNAs encoding proteases with a high degree of similarity to mammalian PC6. Three cDNAs encoding three PC6 isoforms differing only in their carboxy-terminal sequences were found, derived by alternative splicing. Two isoforms appear to be soluble enzymes, whereas the third contains a transmembrane hydrophobic segment and thus is likely to be membrane-bound. All three variants contain many repeats of a cysteine-rich motif that is found in several other PC family members. Thus, amphioxus, like the vertebrates, expresses two types of PCs, e.g., PC2 and PC1/PC3 which function in the regulated secretory pathway in neuroendocrine cells, and the more widely expressed PC6 which functions mainly in the constitutive pathway. 相似文献
78.
Marc A. Martí-Renom José M. Mas Patrick Aloy Enrique Querol Francesc X. Avilés Baldomero Oliva 《Journal of molecular modeling》1998,4(11):347-354
The conformations of protein loops from a non-redundant set of 347 proteins with less than 25% sequence homology have been studied in order to clarify the topological variation of protein loops. Loops have been classified in five types (α-α, α-β, β-α, β-links and β-hairpins) depending on the secondary structures that they embrace. Four variables have been used to describe the loop geometry (3 angles and the end-to-end distance between the secondary structures embracing the loop). Loops with well defined geometry are identified by means of the internal dependency between the geometrical variables by application of information-entropy theory. From this it has been deduced that loops formed by less than 10 residues show an intrinsic dependency on the geometric variables that defines the motif shape. In this interval the most stable loops are found for short connections owing to the entropic energy analysed. 相似文献
79.
Luciana Di Ciero Maria L. V. Oliva Ricardo Torquato Peter Köhler Jürgen K. P. Weder José Camillo Novello Claudio A. M. Sampaio Benedito Oliveira Sergio Marangoni 《Journal of Protein Chemistry》1998,17(8):827-834
Trypsin inhibitors of two varieties of Bauhinia variegata seeds have been isolated and characterized. Bauhinia variegata candida trypsin inhibitor (BvcTI) and B. variegata lilac trypsin inhibitor (BvlTI) are proteins with M
r
of about 20,000 without free sulfhydryl groups. Amino acid analysis shows a high content of aspartic acid, glutamic acid, serine, and glycine, and a low content of histidine, tyrosine, methionine, and lysine in both inhibitors. Isoelectric focusing for both varieties detected three isoforms (pI 4.85, 5.00, and 5.15), which were resolved by HPLC procedure. The trypsin inhibitors show K
i
values of 6.9 and 1.2 nM for BvcTI and BvlTI, respectively. The N-terminal sequences of the three trypsin inhibitor isoforms from both varieties of Bauhinia variegata and the complete amino acid sequence of B. variegata var. candida L. trypsin inhibitor isoform 3 (BvcTI-3) are presented. The sequences have been determined by automated Edman degradation of the reduced and carboxymethylated proteins of the peptides resulting from Staphylococcus aureus protease and trypsin digestion. BvcTI-3 is composed of 167 residues and has a calculated molecular mass of 18,529. Homology studies with other trypsin inhibitors show that BvcTI-3 belongs to the Kunitz family. The putative active site encompasses Arg (63)–Ile (64). 相似文献
80.
Daniela Comegna Monica Benincasa Renato Gennaro Irene Izzo Francesco De Riccardis 《Bioorganic & medicinal chemistry》2010,18(5):2010-2018
The synthesis and screening of neutral and cationic, linear and cyclic peptoids (N-alkylglycine peptidomimetics) is described. Structure–activity relationship studies show that the in vitro activities of the tested peptoids depend on both cyclization and decoration with cationic groups. The most powerful N-lysine cyclopeptoid derivatives showed good antifungal activity against Candida albicans (ATCC90029 and L21) and Candida famata (SA550, Amph B-resistant) and low hemolytic activity. The effects of the cyclic peptoids on membrane permeabilization were evaluated by the propidium iodide exclusion assay. 相似文献