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Krystyna Lesiak Bogdan Uznanski Paul F. Terrence 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):1055-1056
Abstract 2′,5′-Oligoadenylate 5′-triphosphates (2-5A) as products of 2-5A synthetase and activators of ribonuclease L (RNase L), are mediators in one of the mechanisms of interferon′s antiviral action. Upon activation, RNase L inhibits protein synthesis due to the degradation of RNAs. This activity of 2-5A could possibly find an application in virus or cancer chemotherapy, but two major barriers prevent the use of 2′,5′-linked oligoadenylates as therapeutic agents. The 2-5A is readily degraded by a 2′,5′ phosphodiesterase and as a highly negatively charged molecule, is not readily taken up by cells. One possible solution to this latter limitation might be found in chemical modifications of the 2-5A structure. Many analogues of 2-5A have been already obtained with modified base, ribose or phosphate moieties. While these have provided some important information about the enzyme- activator interactions, the cell permeability problem still remains unsolved. One of the major obstacles in this study is lack of a convenient method of synthesis of 2′,5′ ribonucleotides of widely varying structure. 相似文献
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The present paper is the Supplement 2 to the Flora of Xizang, based upon
a collection in 1980 by Mr. W. L. Chen et al. from Mêdog, the south-eastern part of
Xizang. In the paper 11 new species are desribed and 10 new-record species are reported. All the type specimens are kept in the Herbarium of the Institure of Botany,
Academia Sinica (PE). 相似文献
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Partial structure of the human α2(IV) collagen chain and chromosomal localization of the gene (COL4A2) 总被引:3,自引:0,他引:3
Paul D. Killen Clair A. Francomano Yoshihiko Yamada William S. Modi Stephen J. O'Brien 《Human genetics》1987,77(4):318-324
Summary We have isolated a 2.1-kb cDNA clone from a human placental library encoding part of the 2 chain of collagen IV, a major structural protein of basement membranes. The DNA sequence encodes 446 amino acids in the triplehelical domain plus the 227 amino acids of the carboxy-terminal globular domain. The latter structure is composed of two homologous subdomains and is highly conserved between the 1 and 2 chains. The triple-helical domain contained seven interruptions of the Gly-X-Y repeat and these interruptions were in general larger than their counterparts in the 1 chain. DNA from human rodent hybrid cell lines was analyzed under conditions in which there was no cross-hybridization of the 2(IV) cDNA probe with the gene for the 1(IV) collagen chain. An Eco RI fragment characteristic of the 2 chain had a concordance of 0.97 with chromosome 13. This result was confirmed and extended with in situ localization of the gene at 13q34. Since the 1(IV) gene has previously been localized to 13q34, the two type IV collagen genes reside in the same chromosome region (13q34), possibly in a gene cluster. The presence of the genes for type IV collagen chains on chromosome 13 excludes a primary role for these genes in adult polycystic kidney disease and X-linked forms of hereditary nephritis. 相似文献
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Venkataraman Amarnath Traci L. Miller Arthur D. Broom 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,741(2):224-229
Poly(5-fluoro-2′-deoxyuridylic acid) was synthesized and its properties were compared with those of poly(dT) and poly(dU). It readily complexed with poly(dA). The 1:1 complex melted at about 20°C lower than poly(dA) · poly(dT). A triple-stranded helix, poly(dA)·2 poly(dF5U) was formed only in high salt (2.0 M NaCl). 相似文献
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Susmita Borthakur HyeongJu Lee SoonJeung Kim Bing-Cheng Wang Matthias Buck 《The Journal of biological chemistry》2014,289(28):19694-19703
The sterile α motif (SAM) domain of the ephrin receptor tyrosine kinase, EphA2, undergoes tyrosine phosphorylation, but the effect of phosphorylation on the structure and interactions of the receptor is unknown. Studies to address these questions have been hindered by the difficulty of obtaining site-specifically phosphorylated proteins in adequate amounts. Here, we describe the use of chemically synthesized and specifically modified domain-length peptides to study the behavior of phosphorylated EphA2 SAM domains. We show that tyrosine phosphorylation of any of the three tyrosines, Tyr921, Tyr930, and Tyr960, has a surprisingly small effect on the EphA2 SAM structure and stability. However, phosphorylation at Tyr921 and Tyr930 enables differential binding to the Src homology 2 domain of the adaptor protein Grb7, which we propose will lead to distinct functional outcomes. Setting up different signaling platforms defined by selective interactions with adaptor proteins thus adds another level of regulation to EphA2 signaling. 相似文献
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What can venom phospholipases A(2) tell us about the functional diversity of mammalian secreted phospholipases A(2)? 总被引:3,自引:0,他引:3
Most venomous animals including snakes, bees and scorpions contain a variety of venom phospholipases A(2) (vPLA(2)s) which participate in both digestion of prey and venom toxicity. So far, more than 150 vPLA(2)s have been characterized. They all have a conserved fold with several disulfide bridges, can be catalytically active or not, and several of them can display a tremendous array of toxic effects including neurotoxicity and myotoxicity. Furthermore, the molecular diversity of vPLA(2)s found within a single snake venom can result from positive Darwinian selection. Over the last decade, receptors and binding proteins for vPLA(2)s have been identified in mammals, suggesting that vPLA(2)s can exert their toxicities through specific protein-protein interactions, besides their catalytic activity. The brain N-type receptors are involved in the neurotoxicity of vPLA(2)s, but are not yet cloned. The M-type receptor has been cloned from skeletal muscle, belongs to the superfamily of C-type lectins, and interestingly, has homology with vPLA(2) inhibitors purified from snake blood. The molecular diversity of vPLA(2)s and the presence of receptors for vPLA(2)s in mammals raises the possibility that there is also a diversity of mammalian secreted PLA(2)s (msPLA(2)s) which are the normal endogenous ligands of the vPLA(2) receptors. This view led us to clone five novel msPLA(2)s (IID, IIE, IIF, III, and X msPLA(2)s), which together with the previously cloned msPLA(2)s (IB, IIA, IIC, and V), indicate that mammals also express a large diversity of sPLA(2)s. M-type receptors can have IB and IIA msPLA(2)s as natural endogenous ligands, suggesting that msPLA(2)s, like vPLA(2)s, can function as both enzymes and ligands. msPLA(2)s were first implicated in lipid digestion, and more recently in host defense mechanisms including inflammation and antibacterial defense. The growing molecular diversity of msPLA(2)s, which all have a specific tissue distribution, and the presence of receptors suggest that msPLA(2)s, like vPLA(2)s, are endowed with a wide array of biological effects which remain to be discovered. 相似文献
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Jacobsen JR Choi SK Combs J Fournier EJ Klein U Pfeiffer JW Thomas GR Yu C Moran EJ 《Bioorganic & medicinal chemistry letters》2012,22(2):1213-1218
A multivalent approach was applied to the design of long-acting inhaled β(2)-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting β(2)-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C(2)-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection. 相似文献
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Kumi Nagaoka Yoshiaki Kitamura Yoshihito Ueno Yukio Kitade 《Bioorganic & medicinal chemistry letters》2010,20(3):1186-1188
Human ribonuclease L (RNase L), an interferon-induced endoribonuclease, becomes enzymatically active after binding to 2-5A. The 5′-phosphoryl group of 2-5A is reportedly necessary for the conformational change leading to RNase L activation. However, we found that 5′-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at the 2′-terminus were more effective as an activator of RNase L than the parent 2-5A tetramer. Introduction of 8-methyladenosine is thought to induce a dramatic shift of 2-5A in the binding site of RNase L. 相似文献
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H. C. Schröder G. Gosselin J. -L. Imbach W. E. G. Müller 《Molecular biology reports》1984,10(2):83-89
The homogeneous poly(A)-specific 2,3-exoribonuclease from calf thymus gland, which cleaves both 3,5-and 2,5-linked oligoriboadenylates, does not degrade (xyloA2'p)2 xyloA, the xylofuranosyladenosine analogue of the 2-5A core. This oligonucleotide, which is supposed to enter intact cells rapidly, was found to possess an increased stability and an enhanced antiherpesvirus activity compared to the natural (A2'p)2A (Eppstein, D. A., Barnett, J. W., Marsh, Y. V., Gosselin, G. and Imbach, J.-L. (1983) Nature 302, 723–724). The poly(A) anabolic enzyme, poly(A) polymerase (Mn2+-dependent), from the same source, which is initiated by (A3'p)2A and its higher oligomers, does not accept 2–5A core and its xyloadenosine analogue as primer. Both oligonucleotides exert no influence on endoribonuclease IV and on the integrity of the poly(A)-ribonucleoprotein complex.Abbreviations 2-5A
ppp(A2'p)nA(n2). 5-triphospho-oligo [(2–5)adenylyl]adenosine
- 2-5A core
(A2'p)2A, adenylyl(2–5) adenylyl(2–5)adenosine
- xyto 2-tA core
(xyloA2'p)2 xyloA, xyloadenylyl(2–5)xyloadenylyl(2–5)xyloadenosine
The other abbreviations are according to the recommendations of the Commission on Biochemical Nomenclature, see Europ. J. Biochem.15 (1970) 203–208. 相似文献
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Wang Zhong-ren 《植物分类学报:英文版》1997,35(4):317-340
About 300 “species” names of Athyrium from China were published. They are preliminarily treated as 117 species with a number of varieties and hybrids. The complete enumeration will be reported in four parts. The present paper is part one, a key to the species. 相似文献
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Interferons (IFNs) induce a 2′,5′-oligoadenylate (2-5A)-dependent ribonuclease L (RNase L) following virus-infection of mammalian
cells. RNase L degrades both viral and cellular RNAs and restricts virus-proliferation. We have studied organization of RNase
L gene in genomic DNA from the mouse liver by Southern blot analysis. Several BamHI, BglII, EcoRI, HincII, HindIII, NcoI, PstI, SacI, and XbaI restriction fragments hybridized to 32P-labeled mouse RNase L cDNA and the 5′-proximal exon probes. Mouse RNase L gene exists as a single copy (>16 kb DNA) gene.
A 5 kb HindIII and a 2.5 kb EcoRI DNA were detected as 5′-upstream DNA of the gene which may contain mouse RNase L promoter. Our results will help studying
mouse RNase L gene promoter in further details. 相似文献
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E. N. Kalinichenko V. N. Barai S. B. Bokut V. V. Romanova A. I. Zinchenko G. Herrmann I. A. Mikhailopulo 《Biotechnology letters》1989,11(9):621-626
Summary The title compounds were prepared by an enzymatic transdeoxyribosylation from 2 dGuo or 2 dThd to the respective heterocyclic bases, 5-ethyluracil and (E)-5-(2-bromovinyl)uracil, using the whole bacterial cells ofEscherichia coli as a biocatalyst. 相似文献
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Heini Frang Jukka Hellman Adrian Goldman Mika Scheinin Tuomo Glumoff 《Biotechnology letters》2000,22(24):1963-1966
Human 2(C2)-adrenergic receptor was expressed in Escherichia coli as a fusion protein with Bacillus circulans var. alcalophilus cyclomaltodextrin glucanotransferase. For the determination of the expression level (0.6 mg of solubilized fusion protein l–1 of E. coli culture), a two-site immunometric assay based on two monoclonal antibodies with different epitopes was developed. 相似文献