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1.
Abnormal cardiac rhythm in diabetic rats 总被引:1,自引:0,他引:1
A significant occurrence of abnormal rhythm was observed in perfused working hearts of diabetic rats. The incidence of arrhythmias was 19/51 in diabetics as compared with 2/38 in normal controls. In considering possible pathogenetic mechanisms, conduction system defects appear to merit particular attention. 相似文献
2.
Electrical potentials of isolated fat cells 总被引:1,自引:0,他引:1
3.
Leonid Beigelman Alexander Karpeisky Nassim Usman 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):895-899
Abstract The synthesis of phosphoramidites of 6-modified pyrimidine ribonucleosides and their incorporation into hammerhead ribozymes and influence on nuclease stability and catalytic activity is described. 相似文献
4.
Comparison of the hammerhead cleavage reactions stimulated by monovalent and divalent cations 总被引:11,自引:3,他引:8 下载免费PDF全文
O'Rear JL Wang S Feig AL Beigelman L Uhlenbeck OC Herschlag D 《RNA (New York, N.Y.)》2001,7(4):537-545
Although the hammerhead reaction proceeds most efficiently in divalent cations, cleavage in 4 M LiCl is only approximately 10-fold slower than under standard conditions of 10 mM MgCl2 (Murray et al., Chem Biol, 1998, 5:587-595; Curtis & Bartel, RNA, 2001, this issue, pp. 546-552). To determine if the catalytic mechanism with high concentrations of monovalent cations is similar to that with divalent cations, we compared the activities of a series of modified hammerhead ribozymes in the two ionic conditions. Nearly all of the modifications have similar deleterious effects under both reaction conditions, suggesting that the hammerhead adopts the same general catalytic structure with both monovalent and divalent cations. However, modification of three ligands previously implicated in the binding of a functional divalent metal ion have substantially smaller effects on the cleavage rate in Li+ than in Mg2+. This result suggests that an interaction analogous to the interaction made by this divalent metal ion is absent in the monovalent reaction. Although the contribution of this divalent metal ion to the overall reaction rate is relatively modest, its presence is needed to achieve the full catalytic rate. The role of this ion appears to be in facilitating formation of the active structure, and any direct chemical role of metal ions in hammerhead catalysis is small. 相似文献
5.
Karpeisky A Sweedler D Haeberli P Read J Jarvis K Beigelman L 《Bioorganic & medicinal chemistry letters》2002,12(22):3345-3347
2'-Deoxy-2'-N-phthaloyl nucleosides were prepared from arabino nucleosides by triflate displacement with phthalimide in the presence of DBU. The corresponding phosphoramidites suitable for automated oligonucleotide synthesis were also synthesized. The scalability of described procedures was demonstrated on a 100-g scale preparation of 2'-deoxy-2'-amino-C phosphoramidite. 相似文献
6.
Matulic-Adamic J Serebryany V Haeberli P Mokler VR Beigelman L 《Bioconjugate chemistry》2002,13(5):1071-1078
To evaluate potential improvement in tissue specific targeting and cellular uptake of therapeutic ribozymes, we have developed three new phosphoramidite reagents. These reagents can be used in automated solid-phase synthesis to produce oligonucleotide conjugates containing N-acetyl-D-galactosamine (targeting hepatocytes) and folic acid (targeting tumor). N-Acetyl-D-galactosamine was attached through a linker to both 2'-amino-2'-deoxyuridine and D-threoninol scaffolds, and these conjugates were converted to phosphoramidite building blocks. Incorporation of a D-threoninol-based monomer into ribozymes provided multiply labeled ribozyme conjugates. Attachment of the fully protected pteroic acid to the D-threoninol-6-aminocaproyl-L-glutamic acid construct afforded the folic acid conjugate, which was converted into the phosphoramidite and incorporated onto the 5'-end of the ribozyme. 相似文献
7.
Fully protected pA2′p5′A2′p5′A trimers 1a and 1b have been prepared as prodrug candidates for a short 2′‐5′ oligoadenylate, 2‐5A, and its 3′‐O‐Me analog, respectively. The kinetics of hog liver carboxyesterase (HLE)‐triggered deprotection in HEPES buffer (pH 7.5) at 37° has been studied. The deprotection of 1a turned out to be very slow, and 2‐5A never appeared in a fully deprotected form. By contrast, a considerable proportion of 1b was converted to the desired 2‐5A trimer, although partial removal of the 3′‐O‐[(acetyloxy)methyl] group prior to exposure of the adjacent phosphodiester linkage resulted in 2′,5′→3′,5′ phosphate migration and release of adenosine as side reactions. 相似文献
8.
Mikkola Satu Mikhailov Sergey N. Efimtseva Ekaterina Neuvonen Kari Oivanen Mikko Beigelman Leonid Lönnberg Harri 《Origins of life and evolution of the biosphere》2002,32(4):303-310
Stereoisomeric uridylyl(3',5')uridines D,L-UpU andL,D-UpU were synthesised. Their cleavage was followed in thepresence of acid, base and metal ion catalysts to studywhether the stereochemistry affects the inherent reactivity ofthe internucleosidic phosphodiester bond, and whether the lowmolecular weight catalysts can distinguish between thesubstrates. The rate constants obtained were compared to thoseof D,D-UpU. The comparison shows that the stability of thephosphodiester bond does not depend on the stereochemistry ofthe sugar rings. In contrast slight reactivity differences areobserved in the presence of metal ion catalysts, whichsuggests that selective cleavage of stereoisomeric substrateseven by small molecular weight chemical catalysts may bepossible. 相似文献
9.
Leonid Beigelman Alexander Karpeisky Jasenka Matulic-Adamic Carolyn Gonzalez Nassim Usman 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):907-910
Abstract The synthesis of 1-deoxy-D-ribofuranose-3-(2-cyanoethyl N,N-diisopropylphosphoramidite) (6) from D-ribose and its incorporation into a hammerhead ribozyme is described. 相似文献
10.
Use of DNA, RNA, and chimeric templates by a viral RNA-dependent RNA polymerase: evolutionary implications for the transition from the RNA to the DNA world. 下载免费PDF全文
All polynucleotide polymerases have a similar structure and mechanism of catalysis, consistent with their evolution from one progenitor polymerase. Viral RNA-dependent RNA polymerases (RdRp) are expected to have properties comparable to those from this progenitor and therefore may offer insight into the commonalities of all classes of polymerases. We examined RNA synthesis by the brome mosaic virus RdRp on DNA, RNA, and hybrid templates and found that precise initiation of RNA synthesis can take place from all of these templates. Furthermore, initiation can take place from either internal or penultimate initiation sites. Using a template competition assay, we found that the BMV RdRp interacts with DNA only three- to fourfold less well than it interacts with RNA. Moreover, a DNA molecule with a ribonucleotide at position -11 relative to the initiation nucleotide was able to interact with RdRp at levels comparable to that observed with RNA. These results suggest that relatively few conditions were needed for an ancestral RdRp to replicate DNA genomes. 相似文献