N-15 NMR chemical shift changes in the Presence of Mg(H2O)(6)(2+), Zn2+, Cd2+, and Co(NH3)(6)(3+) were used to probe the effect of flanking bases on metal binding sites in three different RNA motifs. We found that: for GC pairs, the presence of a flanking purine creates a site for the soft metals Zn2+ and Cd2+ only; a GG.UU motif selectively binds only Co(NH3)(6)(3+), while a UG.GU motif binds none of these metals; a 3' guanosine flanking the adenosine of a sheared GA.AG pair creates an unusually strong binding site that precludes binding to the cross-strand stacked guanosines within the tandem pair
RNA degradation via the ribonuclease H (RNase H) activity of human immunodeficiency virus type I (HIV-1) reverse transcriptase (RT) is a critical component of the reverse transcription process. In this connection, mutations of RT that inactivate RNase H activity result in noninfectious virus particles. Thus, interfering with the RNase H activity of RT represents a potential vehicle for the inhibition of HIV-1 replication. Here, we demonstrate an approach for inhibiting the RNase H activity of HIV-1 RT by targeting its RNA-DNA hybrid substrates. Specifically, we show that the binding of the 4,5-disubstituted 2-deoxystreptamine aminoglycosides, neomycin, paromomycin, and ribostamycin, to two different chimeric RNA-DNA duplexes, which mimic two distinct intermediates in the reverse transcription process, inhibits specific RT-mediated RNase H cleavage, with this inhibition being competitive in nature. UV melting and isothermal titration calorimetry studies reveal a correlation between the relative binding affinities of the three drugs for each of the chimeric RNA-DNA host duplexes and the relative extents to which the drugs inhibit RT-mediated RNase H cleavage of the duplexes. Significantly, this correlation also extends to the relative efficacies with which the drugs inhibit HIV-1 replication. In the aggregate, our results highlight a potential strategy for AIDS chemotherapy that should not be compromised by the unusual genetic diversity of HIV-1.
Spectroscopic and calorimetric techniques were employed to characterize and contrast the binding of the aminoglycoside paromomycin to three octamer nucleic acid duplexes of identical sequence but different strand composition (a DNA.RNA hybrid duplex and the corresponding DNA.DNA and RNA.RNA duplexes). In addition, the impact of paromomycin binding on both RNase H- and RNase A-mediated cleavage of the RNA strand in the DNA.RNA duplex was also determined. Our results reveal the following significant features: (i) Paromomycin binding enhances the thermal stabilities of the RNA.RNA and DNA.RNA duplexes to similar extents, with this thermal enhancement being substantially greater in magnitude than that of the DNA.DNA duplex. (ii) Paromomycin binding to the DNA.RNA hybrid duplex induces CD changes consistent with a shift from an A-like to a more canonical A-conformation. (iii) Paromomycin binding to all three octamer duplexes is linked to the uptake of a similar number of protons, with the magnitude of this number being dependent on pH. (iv) The affinity of paromomycin for the three host duplexes follows the hierarchy, RNA.RNA > DNA.RNA >> DNA.DNA. (v) The observed affinity of paromomycin for the RNA.RNA and DNA.RNA duplexes decreases with increasing pH. (vi) The binding of paromomycin to the DNA.RNA hybrid duplex inhibits both RNase H- and RNase A-mediated cleavage of the RNA strand. We discuss the implications of our combined results with regard to the specific targeting of DNA.RNA hybrid duplex domains and potential antiretroviral applications.
The halogen-free flame-retarding material with good property satisfying aims of jiuwu project the study and product development of radiation-crosslinking cable and wire materialswas manufactured by choosing basic resin, changing addition amount of flame-ratarding agents, anti-oxygen agents, coupling agents, crosslinking sensitizer and radiation dose.Its rheological property is studied at same time. OI is 40; tensile strength is 11.5MPa; and elongation at break is 370%.
The material is prepared by using low density polyethylene and/or copolymer of ethylene and ethyl acetate as base material and adding antioxidant, cross linking agent, modified inorganic stuffing andother assistant, and through the modification of inorganic stuffing, mixing of the base material, antioxidant and other assistant, mixing of the inorganic stuffing and the mixture while adding cross linking agent for irradiation or chemical cross linking. The material of the present invention has high limited oxygen index, high tensile strength at room temperature, high elongation at rupture and excellent machining fluidity. The present invention changes the surface performance of inorganic stuffing with proper surfactant to raise its affinity to polyolefine and to inhibit the drcrease of cohesion energy density and strengthens the cohesional state of polymer material through cross linking.
Crosslinking is a promising method for stabilizing the electrical properties of polyolefin composites with a positive temperature coefficient of resistivity (PTCR) for application as self-controlled heaters. An interesting phenomenon is that the measured room temperature resistivity of such materials is independent of applied voltage at low DC fields, but crosses over to display an apparent decrease with the accretion of voltage above a critical value. Measured current vs. time of voltage application has been recorded that shows an equilibrium varying with temperature and voltage. Theoretical approaches to these results are discussed.
The electrical resistivity of a radiation-crosslinked polyethylene/carbon black switching composite was investigated as a function of carbon black content and temperature. Carbon blacks of different morphology and microstructure behaved differently regarding the electrical resistivity. A HG black, highly porous and structured, imparts high conductivity to its composite mixture at a low degree of loading, whereas nonporous acetylene EQ black of like structure requires a higher degree of loading to impart the same conductivity. The PTC (positive temperature coefficient) effect anomaly was smaller for HG black than for EQ black. It was found that the PTC anomaly was heightened when a combination of the two different carbon blacks was mixed into the composites. Suggestions as to the causes for this particular behavior are made with reference to the electron micrography and other parameters for microstructure of the two carbon blacks.