Measurements of thermal stability by circular dichroism (CD) spectroscopy have been widely used to assess the binding of peptides to MHC proteins, particularly within the structural immunology community. Although thermal stability assays offer advantages over other approaches such as IC50 measurements, CD-based stability measurements are hindered by large sample requirements and low throughput. Here we demonstrate that an alternative approach based on differential scanning fluorimetry (DSF) yields results comparable to those based on CD for both class I and class II complexes. As they require much less sample, DSF-based measurements reduce demands on protein production strategies and are amenable for high throughput studies. DSF can thus not only replace CD as a means to assess peptide/MHC thermal stability, but can complement other peptide-MHC binding assays used in screening, epitope discovery, and vaccine design. Due to the physical process probed, DSF can also uncover complexities not observed with other techniques. Lastly, we show that DSF can also be used to assess peptide/MHC kinetic stability, allowing a single experimental setup to probe both binding equilibria and kinetics.
A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural α-methylene-β-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the μ-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH(2) (analogue 12) exhibited the highest binding potency (K(i)(μ) = 0.221 nM) and efficacy (EC(50) = 0.0334 nM, E(max) = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the μ-opioid receptor.
By combining the influence of excess alcohol, temperature and monomer-to-initiator ratios in the feed, dinuclear salan aluminum complexes L(R)Al(2)Me(4) exhibited a high degree of control towards the copolymerization of L-LA and ε-CL, producing blocky, gradient, tapered and random copolymers.
Many effective strategies have been developed in order to inhibit the hydrodechlorination in the selective hydrogenation of chloronitrobenzenes to chloroanilines which are important intermediates in the chemistry and industry of dyes, herbicides, pesticides and medicines. However, hydrogenolysis of the carbon-halogen bond as a defect of the hydrogenation process could not be avoided completely over the metal catalysts reported previously, especially at complete conversion of the substrates. Recently we overcame this problem by the invention of nanocomposite catalysts composed of noble metal nanoclusters and inorganic semiconductor nanoparticles. Over these nanocomposite catalysts, the hydrodechlorination of ortho-chloroaniline was completely suppressed even at 100% conversion of ortho-chloronitrobenzene. In this review, we deal with the great efforts and remarkable contributions of different authors during the long exploration for the solutions of this hard obstacle. Stress is placed on supported metal catalysts and polymer-protected metal nanoclusters or colloid catalysts.
a b s t r a c tA three-dimensional numerical approach incorporating the radiation, solar load, and turbine models proposed in this paper was first verified by the experimental data of the Spanish prototype. It then was used to investigate the effects of solar radiation, turbine pressure drop, and ambient temperature on system performance in detail. Simulation results reveal that the radiation model is essential in preventing the overestimation of energy absorbed by the solar chimney power plant (SCPP). The predictions of the maximum turbine pressure drop with the radiation model are more consistent with the experimental data than those neglecting the radiation heat transfer inside the collector. In addition, the variation of ambient temperature has little impact on air temperature rise despite its evident effect on air velocity. The power output of the SCPP within the common diurnal temperature range was also found to be insensitive to ambient temperature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.