Compound prioritization methods increase rates of chemical probe discovery in model organisms

Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ~81,000 compounds in Saccharomyces cerevisiae and identified ~7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ~7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided.     

A pyrene-based fluorescent sensor for Zn2+ ions: a molecular 'butterfly'

A simple pyrene-based triazole receptor has been synthesised and shown to self-assemble in the presence of ZnCl(2) in an exclusively 2:1 ratio, whereas a mixture of 2:1 and 1:1 ratios are observed for other Zn(2+) salts. The pyrene units are syn in orientation; this is supported by a strong excimer signal observed at 410 nm in the presence of ZnCl(2) in acetonitrile. DFT calculations and 2D NMR support the proposed structure.     

BioCD-2008: Synchrotron Radiation Circular Dichroism Spectroscopy of Proteins and Other Biomolecules

A weeklong workshop focusing on circular dichroism (CD) spectroscopy using both conventional and synchrotron sources (SRCD) was presented at the National Synchrotron Light Source at Brookhaven National Laboratory from June 23–27, 2008.     

High resolution emission spectroscopy of the AП-XΣ (red) system of CN

The emission spectra of the A²П-X²Σ⁺ (red) system of ¹²C¹⁴N have been reinvestigated in the 3500-22 000 cm⁻¹ region at high resolution using a Fourier transform spectrometer. In total, spectra of 63 bands involving vibrational levels up to v′ = 22 of the A²П state and v″ = 12 of the X²Σ⁺ ground state have been measured and rotationally analyzed providing an improved set of spectroscopic constants. The present measurements of the Δv = −2 sequence bands of ¹²C¹⁴N and those of ¹³C¹⁴N from Ram et al. (2010) [36] allow for a much improved identification of these two isotopologues in the near infrared spectra of carbon stars.     

Free radicals in pyrimidines: E.S.R. of a γ-irradiated single crystal of 5-nitrouracil

Free radicals are observed in γ-irradiated single crystals of 5-nitrouracil with the unpaired electron showing hyperfine interaction with one nitrogen atom. The principal values of hyperfine coupling are A_x = 22·5 g, A_y = 25·2 g, and A_z = 40·0 g, and the principal values of the spectroscopic splitting factor are g_u = 2·0117, g_v = 2·0064 and g_w = 2·0027. The relationship of the directions of the corresponding principal axes to the molecular orientations show that the unpaired electron must be located in an sp ² orbital on either N₍₁₎ or N₍₅₎. Considerations of the mechanism of radical formation and comparison to radiation damage in other molecules make the N₍₁₎ location seem more probable. The π interaction of the nitro group on C₍₅₎ evidently prevents the formulation of free radicals with the unpaired electron on C₍₅₎. That carbon atom is the most common location of unpaired electron density in other pyrimidine free radicals.