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201.
S. Salvadori R. Guerrini V. Forlani S. D. Bryant M. Attila L. H. Lazarus 《Amino acids》1994,7(3):291-304
Summary Analysis of deltorphin A position 4 analogues included: backbone constrained N
MeHis, spinacine (Spi), N
MePhe and the tetrahydroisoquinoline-3-carboxylic acid (Tic); spatially confined side-chain (Phg); and imidazole alkylation ofl- andd-His4 enantiomers. High selectivity was lost with the following replacements: N
MeHis4, N
MePhe4 and Phg4 reduced binding and the constrained residues also increasedµ binding; ring closure between the side-chain and amino group to yield Spi4 or Tic4 increasedµ affinity. Imidazole methylation of His4 marginally affected opioid binding and doubled selectivity; alkylatedd-His4-derivatives generally maintained selectivity in spite of decreased affinities. Thus, His4 imidazole preserves selectivity by facilitating high binding and by repulsion at theµ receptor. Several low energy conformers of deltorphin A indicated that the His4 imidazole preferred a spatial orientation parallel to the phenolic side-chain of Tyr1 suggestive that this conformation might contribute to high affinity and selectivity. 相似文献
202.
One- and two-dimensional electrophoresis of Nicotiana tabacum pollen and pollen tube proteins confirmed that a new protein is preferentially synthesized during pollen germination and tube growth and becomes the most abundant protein in pollen tubes. Analysis of proteins extracted with sodium dodecyl sulfate (SDS) from different pollen tube fractions showed that it is the most abundant non-covalently bound wall protein, characterized by molecular mass of 69 kDa, pI between 7.9 and 8.2, and glycosylation with glucose and/or mannose. Amino acid analysis revealed relative abundance of serine, glutamic acid and glycine, but did not show the presence of hydroxyproline. According to all these characteristics, it cannot be classified as an extensin-like protein. Another prominent wall-bound glycoprotein has a molecular mass of 66 kDa and the same pI as the 69 kDa glycoprotein. These two glycoproteins are similar also in ConA binding, rate of synthesis, and rapid incorporation into pollen tube walls. Their synthesis is strongly reduced by tunicamycin and this inhibition results in the occurrence of new polypeptides in the range of 57–61 kDa. Tunicamycin also inhibited pollen tube growth. At 10 ng ml-1 and 50 ng ml-1 the inhibitor reduced pollen tube mass after 24 h of culture by 30% and 85%, respectively. This indicates that tobacco pollen presents a system highly sensitive to tunicamycin and that cotranslational N-linked glycosylation on the rough endoplasmic reticulum is required for 66 and 69 kDa glycoprotein formation and for pollen tube growth. Although other proteins appear during pollen germination and tube growth, the new proteins occur at low levels and seem to originate through modifications of preexisting polypeptides. In contrast to 69 and 66 kDa proteins, most proteins detected by [14C]amino acid incorporation and fluorography of gels were not revealed by Coomassie blue staining. 相似文献
203.
Anna Tramontano Elisabetta Bianchi Sara Venturini Franck Martin Antonelo Pessi Maurizio Sallozzo 《Journal of molecular recognition : JMR》1994,7(1):9-24
Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue β-protein aimed at retaining some desirable features of immunogloblin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of main chain conformation of the same regions, based on the ‘canonical structures’ model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical syntyhesis and expression in E. coli and charactgerized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low soubility. We were able to overcome this problem both by further; mutagenesis of the framework and by addition of a solublizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage. 相似文献
204.
A full-length cDNA encoding a human homolog of the 15-kDa subunit (p15) of RNA polymerase II elongation factor SIII was isolated and sequenced. Comparison of the open reading frames of the human p15 cDNA and the previously characterized rat p15 cDNA [Garrett et al., Proc. Natl. Acad. Sci. USA 91 (1994) 5237-5241] indicates that they encode identical proteins and are 93% conserved in nucleotide sequence. 相似文献
205.
Kappei Kobayashi Eriko Ohgitani Yasuyuki Tanaka Masakazu Kita Jiro Imanishi 《Microbiology and immunology》1994,38(4):321-325
The major 70 kDa heat shock protein (HSP70), which is scarcely expressed in unstressed rodent cells, was apparently induced by infection with herpes simplex virus (HSV). Infection with HSV types 1 and 2 elevated HSP70 mRNA levels within 4 hr post-infection. HSP70 synthesis and accumulation increased in HSV-infected cells. Irradiation of HSV with UV-light abolished the ability to induce HSP70 mRNA. Inhibitors of viral DNA synthesis did not affect the induction of HSP70 in infected cells. Protein synthesis within 2 hr after infection was necessary for HSP70 induction. 相似文献
206.
油菜素内酯促进绿豆上胚轴伸长与蛋白质和核酸合成的关系 总被引:3,自引:0,他引:3
用饲喂蛋白质和核酸合成的放射性前体[3 H]-Phe、[3 H]-尿嘧啶和[3 H]-胸腺嘧啶证实了油菜素内酯(BR)能促进绿豆上胚轴的生长和蛋白质、RNA 及DNA 的合成。用蛋白质和核酸合成抑制剂(CH、Act.D、5-Fu)进一步探讨它们对上胚轴伸长的抑制作用与蛋白质、RNA、DNA 和m RNA 合成之间的关系。证明了上胚轴的伸长依赖于蛋白质和核酸的合成,尤其是依赖于m RNA 的合成。说明BR是在转录水平上调节基因的表达,进而促进上胚轴的伸长 相似文献
207.
208.
Millie Hughes-Fulford 《Journal of cellular biochemistry》1994,54(3):265-272
Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the-49 lymphoma variant (cyc?) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc? cells. DNA synthesis is inhibited 42% by dmPGA1 (50 μM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the α,β unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc? cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30–50 μm) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc? cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block. The S-49 cyc? cells are known to have a G1/S boundary through M phase transition time of 14.8 h, making the location of the prostaglandin cell cycle arrest at or very near the G1/S interface. The oncogenes, c-fos and c-myc which are normally expressed during G1 in proliferating cells have a 2–3 fold enhanced expression in prostaglandin G1 arrested cells. These data using the S-49 variants demonstrate that dmPGA1 inhibits DNA synthesis and arrests the cell cycle independent of cAMP-mediated effects. The prostaglandin arrested cells maintain the gene expression of a G1 synchronous cell which suggests a unique molecular mechanism for prostaglandin action in arresting cell growth. These properties indicate that this compound may be an effective tool to study molecular mechanisms of regulation of the cell cycle. 相似文献
209.
Gary L. Johnson Anne M. Gardner Carol Lange-Carter Nan-Xin Qian Marijane Russell Sim Winitz 《Journal of cellular biochemistry》1994,54(4):415-422
Serpentine receptors coupled to the heterotrimeric G protein, Gi2, are capable of stimulating DNA synthesis in a variety of cell types. A common feature of the Gi2-coupled stimulation of DNA synthesis is the activation of the mitogen-activated protein kinases (MAPKs). The regulation of MAPK activation by the Gi2-coupled thrombin and acetylcholine muscarinic M2 receptors occurs by a sequential activation of a network of protein kinases. The MAPK kinase (MEK) which phosphorylates and activates MAPK is also activated by phosphorylation. MEK is phosphorylated and activated by either Raf or MEK kinase (MEKK). Thus, Raf and MEKK converge at MEK to regulate MAPK. Gi2-coupled receptors are capable of activating MEK and MAPK by Raf-dependent and Raf-independent mechanisms. Pertussis toxin catalyzed ADP-ribosylation of αi2 inhibits both the Raf-dependent and-independent pathways activated by Gi2-coupled receptors. The Raf-dependent pathway involves Ras activation, while the Raf-independent activation of MEK and MAPK does not involve Ras. The Raf-independent activation of MEK and MAPK most likely involves the activation of MEKK. The vertebrate MEKK is homologous to the Ste11 and Byr2 protein kinases in the yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. The yeast Ste11 and Byr2 protein kinases are involved in signal transduction cascades initiated by pheromone receptors having a 7 membrane spanning serpentine structure coupled to G proteins. MEKK appears to be conserved in the regulation of G protein-coupled signal pathways in yeast and vertebrates. Raf represents a divergence in vertebrates from the yeast pheromone-responsive protein kinase system. Defining MEKK and Raf as a divergence in the MAPK regulatory network provides a mechanism for differential regulation of this system by Gi2-coupled receptors as well as other receptor systems, including the tyrosine kinases. 相似文献
210.
B. Petersen C. J. Yee W. Bowen R. Zarnegar G. K. Michalopoulos 《Cell biology and toxicology》1994,10(4):219-230
TGF-1 is known as a potent inhibitor of proliferation of rat and human hepatocytes. In this study we show that the effects of TGF-1 are quite different on mouse hepatocytes. In rat and human hepatocytes, TGF-1 inhibited DNA synthesis and also inhibited the morphological changes induced by growth factors in rat and human hepatocytes. In contrast, addition of TGF-1 to mouse hepatocytes resulted in pronounced alterations in morphology of these cells. These changes were similar to those induced by HGF and EGF. The induction of structural changes by TGF-1 was noted only in mouse hepatocytes. Mouse hepatocytes were also much more resistant to the mito-inhibitory effect of TGF-1. These findings suggest profound differences in hepatocyte growth regulation between these species and may relate to observed differences in susceptibility to carcinogenesis.Abbreviations EGF
epidermal growth factor
- HGF
hepatocyte growth factor
- SF
scatter factor
- TGF-1
transforming growth factor beta type one 相似文献