共查询到20条相似文献,搜索用时 0 毫秒
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Development of efficient and safe gene carrier is the main hurdle for successful gene therapy till date. Poor water solubility and low transfection efficiency of chitosan are the main drawbacks to be efficient gene carrier for successful gene therapy. In this work, PAMAM conjugated chitosan was prepared through naphthalimide moiety by simple substitution reaction. The synthesis of the chitosan conjugates was confirmed by FTIR, 1H NMR and XRD analyses. The conjugates showed enhanced DNA binding capability compared to that of unmodified chitosan. Moreover, the conjugates showed minimal cytotoxicity compared to that of polyethyleneimine (PEI, 25 kDa) and also showed good blood compatibility with negligible haemolysis. The transfection efficiency of the conjugate was significantly increased compared to that of unmodified chitosan and it also surpassed the transfection efficiency by PEI. Therefore, PAMAM conjugated chitosan can be used safely as alternate efficient gene delivery vector in gene therapy. 相似文献
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Alireza Najafi Chermhini Mostafa Abedi Hossein Farrokhpour Abbas Teimouri Bahareh Reisi 《Journal of molecular modeling》2013,19(10):4377-4386
The tautomerism of all possible forms of tetrazole selenone (A–G), induced by proton transfer, was studied, theoretically, in different environments including gas phase, continuum solvent and microsolvated environment with one or two explicit water or ammonia molecules. The calculations were performed using two different levels of theory including mPW2PLYP and DFT-B3LYP. The 6-311++G(d,p) basis set was used for C, H, O and N and the standard relativistic effective core pseudo potential LANL2DZ basis set was used for Se atom. It was found that the tetrazole selenone, in the form of A, is the most stable isomer in all of the environments considered in this work. The kinetics of proton transfer reaction was studied in both gas and solvent environments and it was concluded that the activation energy of the reaction increases with going from the gas phase to polar solvents. Moreover, the proton transfer reaction assisted by one or two water or ammonia molecules was investigated and it was found that the activation energy significantly reduces. 相似文献
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Szabó-Plánka T Gyurcsik B Pálinkó I Nagy NV Rockenbauer A Sípoš R Sima J Melník M 《Journal of inorganic biochemistry》2011,105(1):75-83
The complexation of 3-, 4-, and 6-fluorosalicylic acids (HL) with copper(II) was investigated in aqueous solution by pH-potentiometry combined with UV-visible spectrophotometry, and in 50 v/v % water-methanol mixture by the two-dimensional ESR simulation method. Both methods showed the formation of [CuLH−1] and [CuL2H−2]2− of high stabilities, and, at low excess of ligand, the ESR-silent mixed hydroxido complex [Cu2L2H−3]−. Further species were also identified by the two-dimensional ESR simulation method: [CuL]+ in the acidic region, the minor dimer [Cu2L2H−2], and the cis and the trans isomers for [CuL2H−2]2−. The position of the fluorine atom in the aromatic ring had significant effect on the coordination abilities of the ligands, in good correlation with their reported biological activities. It was 3-fluorosalicylic acid, which formed the most stable complexes [CuLH−1] and [CuL2H−2]2−, while the mononuclear complexes with 6-fluorosalicylic acid were found to be the least stable. For the other ligands (including 5-fluorosalicylic acid studied recently), complexes of medium stabilities were formed. For the interpretation of these findings, ab initio and semi-empirical quantum chemical calculations were carried out for the ligand molecules, isolated and surrounded by water molecules, respectively. 相似文献
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Łodyga-Chruścińska E Sanna D Micera G Chruściński L Olejnik J Nachman RJ Zabrocki J 《Acta biochimica Polonica》2006,53(1):65-72
The aim of the investigation was to establish the chelating ability of a new proctolin analogue of the sequence Arg-Tyr-LeuPsi[CN(4)]Ala-Thr towards copper(II) ions. The insertion of the tetrazole moiety into the peptide sequence has considerably changed the coordination ability of the ligand. Potentiometric and spectroscopic (UV-Vis, CD, EPR) results indicate that the incorporation of 1,5-disubstituted tetrazole ring favours the formation of a stable complex form of CuH(-1)L. This 4N coordination type complex is the dominant species in the physiological pH range. The tetrazole moiety provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside the peptide backbone. These findings suggest that Cu(II) can hold peptide chains in a bent conformation. This bent conformation may be essential for bioactivity of the tetrazole peptides. 相似文献
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Three cationic lipids derived from [12]aneN3 modified with naphthalimide (1a), oleic acid (1b) and octadecylamine (1c) were designed and synthesized. In vitro transfection showed that all these liposomes can deliver plasmid DNA into the tested cell lines. Among these liposomes, 1a gave the best transfection efficiency (TE) in A549 cells, which was higher than that of lipofectamine 2000. More importantly, the TE of 1a was dramatically increased in the presence of 10% serum. These results suggested that 1a might be a promising non-viral gene vector, and also give further insight for developing novel high performance gene delivery agents. 相似文献
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Effect of target secondary structure on RNAi efficiency 总被引:4,自引:0,他引:4
Shao Y Chan CY Maliyekkel A Lawrence CE Roninson IB Ding Y 《RNA (New York, N.Y.)》2007,13(10):1631-1640
RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) has become a powerful tool for gene knockdown studies. However, the levels of knockdown vary greatly. Here, we examine the effect of target disruption energy, a novel measure of target accessibility, along with other parameters that may affect RNAi efficiency. Based on target secondary structures predicted by the Sfold program, the target disruption energy represents the free energy cost for local alteration of the target structure to allow target binding by the siRNA guide strand. In analyses of 100 siRNAs and 101 shRNAs targeted to 103 endogenous human genes, we find that the disruption energy is an important determinant of RNAi activity and the asymmetry of siRNA duplex asymmetry is important for facilitating the assembly of the RNA-induced silencing complex (RISC). We estimate that target accessibility and duplex asymmetry can improve the target knockdown level significantly by nearly 40% and 26%, respectively. In the RNAi pathway, RISC assembly precedes target binding by the siRNA guide strand. Thus, our findings suggest that duplex asymmetry has significant upstream effect on RISC assembly and target accessibility has strong downstream effect on target recognition. The results of the analyses suggest criteria for improving the design of siRNAs and shRNAs. 相似文献
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Katsuhiro Kawashiro Hideki Sugahara Tomoya Tsukioka Shigeru Sugiyama Hiromu Hayashi 《Biotechnology letters》1996,18(12):1381-1386
Summary The -chymotrypsin-catalyzed transesterification between a racemic JV-trifluoroacetyl-phenylalanine ester and 1-propanol, was carried out in organic media. Although activation of the substrate by introducing electron-withdrawing group to the ester moiety enhanced the rate of reaction, it decreased enantioselectivity at the same time. In the instance of subtilisin Carlsberg, inversion of the L-specificity was observed. 相似文献
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Effect of cellular physiology on PCR amplification efficiency 总被引:1,自引:0,他引:1
Culture conditions, and other variables that modulate a cell's physiology, can bias a polymerase chain reaction (PCR) amplification against generating a representative population profile. Two Pseudomonas putida nahR alleles were constructed in pUC19 that differ solely in a 31-bp internal segment whose sequence has been inverted. After PCR amplification, the products could be distinguished on the basis of a change in a unique restriction site. When an Escherichia coli strain carrying one nahR allele is submitted to different growth conditions, the consequences of such variations on the relative PCR amplification of whole cells can be ascertained through coamplification with a strain carrying the other allele and subsequent restriction analysis. Cells in stationary phase displayed improved amplifiability while cells grown at 42°C were equally amplifiable as compared to cells grown at 37°C. However, sublethal levels of tetracycline or growth in minimal medium made the PCR target in these cells relatively less amplifiable. When cells are completely lysed and the plasmid DNA is purified beforehand, the coamplification bias is eliminated. These results suggest that mixed populations containing cells in different physiological states may not be representatively amplified by PCR unless a DNA extraction step is included. 相似文献
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Nickel cytochrome c has been synthesized by the reaction of metal-free porphyrin cytochrome c with Ni(II) ions in 0.6 Mglycylglycine and 4 M KSCN. Electronic spectra and susceptibility measurement showed the nickel to be in a high-spin octahedral configuration exemplifying the strong influence of the protein moiety as a macrocyclic ligand on the coordination chemistry of the metal ion. Nickel cytochrome c has the same electrophoretic mobility, helicity and pK values of conformational transitions as the native enzyme. At high pH, the partially denatured nickel cytochrome c becomes dimeric. Nitric oxide reacts with nickel cytochrome c to form the nitrosyl derivative with (formula: see text). Reaction of NO with nickel protoporphyrin IX dimethyl ester in toluene, pyridine, or methylthioethanol produced no stable nitrosyl products, clearly demonstrating the effect of protein on metal ion ligation. 相似文献
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Yang Dingjian Wang Rui Ma Yaping Di Yujun Huo Xiaofeng 《International journal of peptide research and therapeutics》1999,6(5-6):391-394
Summary Deltorphin II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly, NH2, Del II), an endogenous linear heptapeptide, is a highly selective agonist of the δ-opioid receptor. To study the effect
of the position 4 residue (Glu) on the opioid activity of Del II, we designed and synthesized three analogues of Del II by
solid-phase peptide synthesis. They were [Val4, Glu5]Del II, [Val4, Glu6]Del II and [Gly4, Glu7]Del II. To study the effect of spin labeling on peptide bioactivities, all the peptides were labeled using a free radical.
The labeling material was a stable nitrogen-oxygen free radical which was linked to the N-terminal via an amide bond. We investigated
the opioid bioactivities of these analogues both in vivo and in vitro, and concluded that the differences in opioid activity
of Del II and its analogues were due to structural differences. When the Glu residue is at position 5 or 6, the internal hydrogen
bonds in Del II are affected and there is a change in three-dimensional structure and opioid activity. The antinociceptive
activity of all the peptides decreased after spin labeling. This indicates that the stable nitrogen-oxygen free radical is
a dual-function spin-labeling molecule. 相似文献
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Kazuaki Harata 《Bioorganic chemistry》1980,9(4):530-539
Circular diochroism (CD) spectra of four p-nitrophenyl glycosides and their cycloamylose complexes were investigated at various concentrations of cycloamylose and at temperatures ranging from 20 to 60°C. The CD spectra of p-nitrophenyl glycosides changed remarkably in the presence of cycloamyloses, and significant differences in spectral shape and intensity were observed between the cyclohexaamylose complex and the cycloheptaamylose complex. The difference CD spectra between the free guest and its complex indicates that the nitrophenyl group is included in the cycloamylose cavity but its disposition is different between the complexes with cyclohexaamylose and cycloheptaamylose. Values of enthalpy and entropy of the cyclohexaamylose complex are considerably larger than those of the corresponding cycloheptaamylose complex, although the free energy differs only slightly. It is suggested that the nitrophenyl group is more loosely bound to the cycloheptaamylose cavity than to the cyclohexaamylose cavity, and has much more flexibility in its disposition. 相似文献
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D. N. Silachev E. A. Usatikova I. B. Pevzner L. D. Zorova V. A. Babenko M. V. Gulyaev Yu. A. Pirogov E. Yu. Plotnikov D. B. Zorov 《Biochemistry. Biokhimii?a》2017,82(9):1006-1016
Remote ischemic preconditioning of hind limbs (RIPC) is an effective method for preventing brain injury resulting from ischemia. However, in numerous studies RIPC has been used on the background of administered anesthetics, which also could exhibit neuroprotective properties. Therefore, investigation of the signaling pathways triggered by RIPC and the effect of anesthetics is important. In this study, we explored the effect of anesthetics (chloral hydrate and Zoletil) on the ability of RIPC to protect the brain from injury caused by ischemia and reperfusion. We found that RIPC without anesthesia resulted in statistically significant decrease in neurological deficit 24 h after ischemia, but did not affect the volume of brain injury. Administration of chloral hydrate or Zoletil one day prior to brain ischemia produced a preconditioning effect by their own, decreasing the degree of neurological deficit and lowering the volume of infarct with the use of Zoletil. The protective effects observed after RIPC with chloral hydrate or Zoletil were similar to those observed when only the respective anesthetic was used. RIPC was accompanied by significant increase in the level of brain proteins associated with the induction of ischemic tolerance such as pGSK-3β, BDNF, and HSP70. However, Zoletil did not affect the level of these proteins 24 h after injection, and chloral hydrate caused increase of only pGSK-3β. We conclude that RIPC, chloral hydrate, and Zoletil produce a significant neuroprotective effect, but the simultaneous use of anesthetics with RIPC does not enhance the degree of neuroprotection. 相似文献
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P A Temussi D Picone T Tancredi R Tomatis S Salvadori M Marastoni G Balboni 《FEBS letters》1989,247(2):283-288
Deltorphin is an opioid peptide with the sequence H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, recently isolated from the skin of Phyllomedusa sauvagei. Its enormous selectivity towards the delta-opioid receptor and the similarity of the N-terminal part of the sequence with that of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), a mu selective peptide isolated from the same natural source, prompted a comparative conformational study. A 1H-NMR study in two different solvent systems showed that the conformational preferences of the N-terminal sequences of the two peptides are similar. The different selectivities towards opioid receptors have been interpreted in terms of charge effects. Besides a general trend consistent with the role of the membrane in the preselection of the peptides, the present study demonstrates the crucial role played by charged residues in the interaction inside the receptors. 相似文献