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961.
Moon Woo Chun Sung Pil Choi Myong Jung Kim Chol Joon Bae Hyung Ryong Moon Hee-Doo Kim 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):615-616
Abstract Novel 1,3-oxathiolanyl pyrimidine nucleosides with 5-hydroxymethyl substituent were synthesized starting from d-mannose and evaluated for antiviral activities against HIV-1, HSV type 1,2 and HCMV. 相似文献
962.
Chang Hyun Oh Lian Jin Liu Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(10):721-733
A novel 3′,4′-dimethyl-5′-norcarbocyclic adenosine phosphonic acid was prepared using acyclic stereoselective route from 4-hydroxybutan-2-one (4). To improve the cellular permeability and enhance the anti-HIV activity of this phosphonic acid, a (bis)SATE phosphonodiester nucleoside prodrug (20) was prepared and its chemical stability was evaluated. The newly synthesized bis(SATE) analogue (20) and its parent nucleoside phosphonic acid (18) were assayed for anti-HIV activity using an in vitro assay system in a CEM cell line. 相似文献
963.
Sarah C. Zimmermann Joshua M. Sadler Peter I. O’Daniel Nathaniel T. Kim Katherine L. Seley-Radtke 《Nucleosides, nucleotides & nucleic acids》2013,32(3):137-154
A series of flexible carbocyclic pyrimidine nucleosides has been designed and synthesized. In contrast to previously reported “fleximers” from our laboratory, these analogues have the connectivity of the heterocyclic base system “reversed”, where the pyrimidine ring is attached to the sugar moiety, rather than the five membered imidazole ring. As was previously seen with the ribose fleximers, their inherent flexibility should allow them to adjust to enzyme binding site mutations, as well as increase the affinity for atypical enzymes. Preliminary biological screening has revealed surprising inhibition of adenosine deaminase, despite their lack of resemblance to adenosine. 相似文献
964.
The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 5 ′-deoxyversions of threosyl phosphonate nucleosides from 1,4-dihydroxy-2-butene. The synthesized nucleoside phosphonic acid analogues 14 and 19 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 14 exhibits moderate in vitro anti-HIV-1 activity (EC50 = 12.6 μM). 相似文献
965.
966.
Shuying Yang Yi‐Ping Li Tongjun Liu Xiaoning He Xue Yuan Chunyi Li Jay Cao Yunjung Kim 《Genesis (New York, N.Y. : 2000)》2013,51(3):201-209
Regulators of G‐protein Signaling (Rgs) proteins are the members of a multigene family of GTPase‐accelerating proteins (GAP) for the Galpha subunit of heterotrimeric G‐proteins. Rgs proteins play critical roles in the regulation of G protein couple receptor (GPCR) signaling in normal physiology and human diseases such as cancer, heart diseases, and inflammation. Rgs12 is the largest protein of the Rgs protein family. Some in vitro studies have demonstrated that Rgs12 plays a critical role in regulating cell differentiation and migration; however its function and mechanism in vivo is largely unknown. Here, we generated a floxed Rgs12 allele (Rgs12flox/flox) in which the exon 2, containing both PDZ and PTB_PID domains of Rgs12, was flanked with two loxp sites. By using the inducible Mx1‐cre and Poly I:C system to specifically delete Rgs12 at postnatal 10 days in interferon‐responsive cells including monocyte and macrophage cells, we found that Rgs12 mutant mice had growth retardation with the phenotype of increased bone mass. We further found that deletion of Rgs12 reduced osteoclast numbers and had no significant effect on osteoblast formation. Thus, Rgs12flox/flox conditional mice provide a valuable tool for in vivo analysis of Rgs12 function and mechanism through time‐ and cell‐specific deletion of Rgs12. genesis 51:201–209, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
967.
Christine Gersch Sergiu P. Palii Kyung Mee Kim Alexander Angerhofer Richard J. Johnson George N. Henderson 《Nucleosides, nucleotides & nucleic acids》2013,32(8):967-978
The 1980 identification of nitric oxide (NO) as an endothelial cell-derived relaxing factor resulted in an unprecedented biomedical research of NO and established NO as one of the most important cardiovascular, nervous and immune system regulatory molecule. A reduction in endothelial cell NO levels leading to “endothelial dysfunction” has been identified as a key pathogenic event preceding the development of hypertension, metabolic syndrome, and cardiovascular disease. The reduction in endothelial NO in cardiovascular disease has been attributed to the action of oxidants that either directly react with NO or uncouple its substrate enzyme. In this report, we demonstrate that uric acid (UA), the most abundant antioxidant in plasma, reacts directly with NO in a rapid irreversible reaction resulting in the formation of 6-aminouracil and depletion of NO. We further show that this reaction occurs preferentially with NO even in the presence of oxidants peroxynitrite and hydrogen peroxide and that the reaction is at least partially blocked by glutathione. This study shows a potential mechanism by which UA may deplete NO and cause endothelial dysfunction, particularly under conditions of oxidative stress in which UA is elevated and intracellular glutathione is depleted. 相似文献
968.
On the basis of the discovery that the threosyl nucleoside phosphonate PMDTA is a potent anti-HIV compound, we synthesized several 4′-trifluoromethyl-5′-deoxyapiosyl nucleoside phosphonic acids and evaluated their anti-HIV activity. An efficient synthetic route was optimized, starting from an α-trifluoromethyl-α,β-unsaturated ester. Glycosylation of the purine nucleosidic bases with a glycosyl donor yielded modified nucleoside intermediates, which were then phosphonated and hydrolyzed to provide the targeted nucleoside analogs. Once synthesized, the anti-HIV and cytotoxic activities of each analog were evaluated. None of the analogs showed significant anti-HIV activity at concentrations up to 100 μM. 相似文献
969.
Chang Hyun Oh Jin Woo Kim Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(8):871-878
Novel vinyl branched apiosyl nucleosides were synthesized in this study. Apiosyl sugar moiety was constructed by sequential ozonolysis and reductions. The bases (uracil and thymine) were efficiently coupled by glycosyl condensation procedure (persilyated base and TMSOTf). The antiviral activities of the synthesized compounds were evaluated against the HIV-1, HSV-1, HSV-2, and HCMV. Compound 10β displayed moderate anti-HIV activity (EC50 = 17.3 μg/mL) without exhibiting any cytotoxicity up to 100 μM. 相似文献
970.