Tandem thiol switch synthesis of peptide thioesters via N-S acyl shift on thiazolidine

An efficient "thiol switch" approach for the synthesis of peptide thioesters via an acid-catalyzed N-S acyl shift and a thioester exchange reaction in tandem with concurrent removal of protecting groups is described. This method employs novel 2-(thiomethyl)thiazolidine (TMT)-anchored resins and is fully compatible with Fmoc chemistry.     

Examining the mechanism of action of a kinesin inhibitor using stable isotope labeled inhibitors for cross-linking (SILIC)

It is difficult to determine a chemical inhibitor's binding site in multiprotein mixtures, particularly when high-resolution structural studies are not straightforward. Building upon previous research involving photo-cross-linking and the use of mixtures of stable isotopes, we report a method, Stable Isotope Labeled Inhibitors for Cross-linking (SILIC), for mapping a small molecule inhibitor's binding site in its target protein. In SILIC, structure-activity relationship data is used to design inhibitor analogues that incorporate a photo-cross-linking group along with either natural or 'heavy' stable isotopes. An equimolar mixture of these inhibitor analogues is cross-linked to the target protein to yield a robust signature for identifying inhibitor-modified peptide fragments in complex mass spectrometry data. As a proof of concept, we applied this approach to an ATP-competitive inhibitor of kinesin-5, a widely conserved motor protein required for cell division and an anticancer drug target. This analysis, along with mutagenesis studies, suggests that the inhibitor binds at an allosteric site in the motor protein.     

Subcellular localization of early biochemical transformations in cancer-activated fibroblasts using infrared spectroscopic imaging

The tumor microenvironment, or stroma, is chemically and morphologically modified during carcinoma progression. The predominant cell type in the stroma, the fibroblast, maintains collagen properties in normal tissue and often transformed during tumor progression. Biochemical changes within fibroblasts upon initial cancer activation, however, are relatively poorly defined. Here, we hypothesized that Fourier transform infrared (FT-IR) spectroscopic imaging could potentially be employed to examine these early transformations. Further, we employ attenuated total reflectance (ATR) microscopy to characterize subcellular spectra and their changes upon transformation. We characterized fibroblast transitions upon stimulation with both a molecular agent and a carcinoma-mimicking cellular co-culture system. Changes were predominantly observed in the 1080 cm(-1) and 1224 cm(-1) peak absorbance, commonly associated with nucleic acids, as well as in the band at 2930 cm(-1) associated with the C-H stretching of proteins in the cytoplasmic compartment. In conclusion, biochemical changes in cancer-associated fibroblasts that express α-SMA are dominated by the cytoplasm, rather than the nucleus. This ensures that spectral changes are not associated with proliferation or cell cycle processes of the cells and the cells are undergoing a true phenotypic change denoted by protein modifications in the cell body.     

Characterization of porcine skin as a model for human skin studies using infrared spectroscopic imaging

Porcine skin is often considered a substitute for human skin based on morphological and functional data, for example, for transdermal drug diffusion studies. A chemical, structural and temporal characterization of porcine skin in comparison to human skin is not available but will likely improve our understanding of this porcine skin model. Here, we employ Fourier transform infrared (FT-IR) spectroscopic imaging to holistically measure chemical species as well as spatial structure as a function of time to characterize porcine skin as a model for human skin. Porcine skin was found to resemble human skin spectroscopically and differences are elucidated. Cryo-prepared fresh porcine skin samples for spectroscopic imaging were found to be stable over time and small variations are observed. Hence, we extended characterization to the use of this model for dynamic processes. In particular, the capacity and stability of this model in transdermal diffusion is examined. The results indicate that porcine skin is likely to be an attractive tool for studying diffusion dynamics of materials in human skin.     

Finite p-groups with non-cyclic center have a non-inner automorphism of order p

Archiv der Mathematik - Let G be a finite non-abelian p-group and let $$W(G)/Z(G)=\Omega _1(Z_2(G)/Z(G))$$ . A longstanding conjecture asserts that G admits a non-inner automorphism of order p. We...     

Sub-barrier fission fragment angular distributions for the system19F+232Th

The measurements of fission fragment angular distributions for the system¹⁹F+²³²Th have been extended to the sub-barrier energies of 89.3, 91.5 and 93.6 MeV. The measured anisotropies, within errors are nearly the same over this energy region. However, the deviation of the experimental values of anisotropies from that of standard statistical model predictions increases as the bombarding energy is lowered.     

Theoretical expression for change of extraordinary refractive index in annealed proton exchanged LiNbO3 optical waveguides

A general expression for the change in extraordinary refractive index of the annealed proton exchanged LiNbO₃ waveguide has been deduced. The expression deduced explains the experimental results of decrease in change of extraordinary refractive index with annealing. The effect of annealing time has also been incorporated following Cao's model (Cao, Ramaswamy, Srivastava, J. Lightwave Technol. 10 (1992) 1302–1313). The concentration profile of protons in the annealed waveguide has been deduced theoretically, which is consistent with the previous results. The spontaneous polarization has been considered as the central mechanism for change in extraordinary refractive index due to proton exchange with annealing.     

The transition from bulk to nano as a phase transition

It is demonstrated that the chemical potential of bosons trapped in a harmonic potential shows a discontinuity as a function of the number of particles in the system. In the model used, it is shown that if the number of particles is of the order of 10⁶ or greater, bulk-like behaviour is exhibited by the system. This translates to a ratio of V/V_c>10⁶ for bulk behaviour, where V is the crystallite volume of the experimental sample and V_c is the volume of the unit cell. Several experimental results covering a wide range of physical phenomena that corroborate the fact that such a number-induced phase transition indeed exists are presented.     

Synthesis of nanosized silver colloids by microwave dielectric heating

Silver nanosized crystallites have been synthesized in aqueous and polyols viz., ethylene glycol and glycerol, using a microwave technique. Dispersions of colloidal silver have been prepared by the reduction of silver nitrate both in the presence and absence of stabilizer poly(vinylpyrolidone) (PVP). It was observed that PVP is capable of complexing and stabilizing Ag nanoparticles formed through the reduction of Ag⁺ ions in water and ethylene glycol. In the case of ethylene glycol, it has been shown that the use of PVP leads to particles with a high degree of stability. The colloids are stable in glycerol for months even in the absence of stabilizer.