Flaviviruses cause many human diseases, including dengue fever, yellow fever, West Nile viral encephalitis, and hemorrhagic fevers, and are transmitted to their vertebrate hosts by infected mosquitoes and ticks. Domain III of the envelope protein (E-D3) is considered to be the primary viral determinant involved in the virus-host-cell receptor interaction, and thus represents an excellent target for antiviral drug development. Langat (LGT) virus is a naturally attenuated BSL-2 TBE virus and is a model for the pathogenic BSL-3 and BSL-4 viruses in the serogroup. We have determined the solution structure of LGT-E-D3 using heteronuclear NMR spectroscopy. The backbone dynamics of LGT-E-D3 have been investigated using 15 N relaxation measurements. A detailed analysis of the solution structure and dynamics of LGT-E-D3 suggests potential residues that could form a surface for molecular recognition, and thereby represent a target site for antiviral therapeutics design.
The Caenorhabditis elegans SEM-5 SH3 domains recognize proline-rich peptide segments with modest affinity. We developed a bivalent peptide ligand that contains a naturally occurring proline-rich binding sequence, tethered by a glycine linker to a disulfide-closed loop segment containing six variable residues. The glycine linker allows the loop segment to explore regions of greatest diversity in sequence and structure of the SH3 domain: the RT and n-Src loops. The bivalent ligand was optimized using phage display, leading to a peptide (PP-G 4 -L) with 1000-fold increased affinity for the SEM-5 C-terminal SH3 domain over that of a natural ligand. NMR analysis of the complex confirms that the peptide loop segment is targeted to the RT and n-Src loops and parts of the -sheet scaffold of this SH3 domain. This binding region is comparable to that targeted by a natural non-PXXP peptide to the p67 phox SH3 domain, a region not known to be targeted in the Grb2 SH3 domain family. PP-G 4 -L may aid in the discovery of additional binding partners of Grb2 family SH3 domains.
ABSTRACT:Acrylamide/ethyl acrylate (A/E) and acrylamide/butyl acrylate (A/B) copolymers were prepared by free radical solution polymerization. Copolymer composition was determined from the nitrogen content of the copolymers. The copolymer composition data were used to determine the reactivity ratios for the copolymerization of A/E and A/B copolymer systems by Kclcn-Tiidos (KT) and nonlinear error in variables (EVM) methods. The reactivity ratios obtained are r A= 0.59 ± 0.05 and re=0.91±0.09 for A/E copolymer system and rA=0.71±0.05 and r8 =1.27±0.08 for A/B copolymer system. Microstructures in terms of the triad distribution from 13 C NMR spectroscopy were found to be in good agreement with those calculated from the theoretical models and Monte Carlo (MC) simulations. MC simulations were also used to determine the degree of polymerization of the two copolymer systems.KEY WORDS Microstructure / Acrylamide/Alkyl Acrylate Copolymers/ Nuclear Magnetic Resonance Spectroscopy / Monte Carlo Simulations / Detailed understanding of the microstructure of synthetic vinyl polymers is of fundamental and practical significance. The macroscopic physicomechanical and physicochemical properties of these materials are inherently dependent on chain microstructures. 1 • 2 Various mechanical properties of the polymers like viscous flow, refractive index, thermal expansivity, crystallization, etc. depend on the Tg of the polymers which in turn is affected by pendant groups and sequence distribution of comonomer units. 3 · 4 Acrylamide polymers are an important class of materials because of their use in many industrial applications such as base and top coats in leather industry,5 flocculants in industrial wastes, papermaking and mining, etc. Many workers have reported the reactivity ratios and microstructures of acrylamide copolymers by 1 H and 13 C NMR spectroscopy. 6 -9 The acrylamide/ethyl acrylate (A/E) and acrylamide/butyl acrylate (A/B) copolymers were synthesised by solution polymerization. The reactivity ratios and comonomer sequence distribution of A/E and A/B copolymers using 13 C NMR spectroscopy is reported in this article. EXPERIMENT ALEthyl acrylate (Central Drug House, India) and butyl acrylate (Central Drug House, India) were distilled under reduced pressure and stored below 5°C. Acrylamide (Sisco Research Laboratories, India) was recrystallized twice from chloroform. N,N-Dimethyl formamide (DMF) (Merck, Germany) was distilled and dried.A series of A/E and A/B copolymers containing different mole percent of the respective comonomers in feed were prepared by solution polymerization in DMF at 65°C using benzoyl peroxide (0.5 w/v%) as the initiator. The conversion was kept below 10% by precipitating the copolymer in water. The copolymers t To whom all correspondence should be addressed. 664were further dissolved in DMF and reprecipitated in water and vacuum dried.The copolymer composition was determined by estimating the nitrogen content of the copolymers. The C, H, and N analyses were done on a Perkin-Elmer 240C Elemen...
Acrylamide/vinyl acetate copolymers were prepared by solution polymerization using benzoyl peroxide as the initiator. The copolymer composition was determined from the percent nitrogen in the copolymers. The comonomer reactivity ratios determined using Kelen−Tudos and nonlinear error-in-variable methods are r A = 9.28 ± 0.6 and r V = 0.09 ± 0.006. The triad sequence distributions in terms of A- and V-centered triads have been obtained from 13C{H} NMR spectra of the copolymers. The methine and the methylene carbon signals were assigned to compositional (triad, tetrads, and pentads) and configurational (triads) sequences. The broad and overlapping 1H NMR spectra were assigned with the help of 2D inverse-HETCOR and TOCSY experiments.
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