X-ray screens

A series of powder photographs was taken in a Norelco camera 360 mm. in circumference which holds the film in the Straumanis arrangement and permits a maximum Bragg angle of 87-6°. The copper K radiation was filtered through 0-001 in. nickel foil. Eastman No-Screen X-ray film was used throughout. All photographs were taken at room temperature, 26 + 2° C. 

There are various methods to conduct a fragment screening campaign. The most commonly utilized methods include various NMR techniques, mass spectrometry, SPR, and biochemical screens. X-ray crystallization is a preferred method since it provides a binding conformation, but can only be used when the target protein is well behaved. Various calorimetry techniques have also been used for fragment screening, but these have been less commonly utilized. The merits of each method have been discussed in the literature (26) and will not be outlined here. 

In preparation for XRD, 0.50 g samples were placed in platinum pans and heated at 10°C/min in a furnace where the control thermocouple was in contact with the specimen container. Specimens were quenched by immediate exposure to room temperature then ground with a mortar and pestle to pass through a 325 mesh screen. X-ray diffraction was performed using a Philips9 x-ray diffractometer. Diffraction patterns were obtained with 29 values ranging from 20° to 60° 29. The diffracted x-rays were counted over 0.02° intervals for 2... 

In a number of experiments studying the incorporation of S3504 into seromucoid fractions 10-/il. samples of plasma were applied to paper strips and subjected to electrophoresis in the Beckman-Spinco paper electrophoresis apparatus. The resultant oven-dried paper strips were attached to an 8 x 10 sheet of paper and applied directly to a sheet of Eastman No-screen x-ray film. Exposure extended over a period of 1 month. At the end of this time the film was developed in the usual manner (see Figure 2). The paper strips were then stained with bromophe-nol blue to demonstrate the major protein fractions. 

We have used a highly structure-driven approach composed of fragment-based NMR screening, X-ray crystallography, and structure-assisted chemistry to develop a first-in-class clinical candidate as a potential proof-of-concept for the inhibition of BACE-1 in AD. Crucial to this achievement was the initial identification of a ligand-efficient isothiourea fragment and its X-ray crystal structure, which revealed an extensive H-bond network with the two active site aspartates. This interaction was unprecedented in the aspartic acid protease field when we discovered it several... 

A specific example will be useful. The DQE is graphed in figure 5.20 for Kodak No-Screen X-ray film (from Gruner, Milch and Reynolds (1978)) ... 

Radioluminescence (Prompt) X-ray screen, x-ray scintillators, scintillation detectors... 

Autoradiography has been extensively used to locate radioactive areas on chromatograms. Usually the chromatogram is pressed against a no-screen X-ray film and allowed to develop. The development time can extend over a period of weeks or months, which allows radioactive areas of very low activity to be detected. ... 

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