SAR by MS

Fig. 10.8 SAR by MS applied to the A1061 construct (see text), (a) Structures of key motifs screened against the RNA target. Compound A is a D-amino acid. Compounds B1 and B2 are quinoxalin-2,3-diones. Compound AB is the rigid biaryl linked compound, (b) Binding affinity for the motifs when screened individually as well as binding affinity for motifs when screened in competition experiments are shown. Binding...

SAR by MS a ligand based technique for drug lead discovery against structured RNA targets. J Med Chem 2002, 45, 3816-3819. 

Structure-activity relationships by mass spectrometry (SAR by MS) finds high-affinity ligands... 

FIGURE 2.5 Schematic diagram for iteratively finding higher-affinity RNA ligands with SARs, with FTICR-MS as the detector, a technique referred to as SAR by MS. (Reprinted from Borman [29], used with permission. Copyright 2000 by the American Chemical Society.)... 

Swayze, E.E., Jefferson, E.A., Sannes-Lowery KA., Blyn, L.B., Risen, L.M., Arakawa, S., Osgood, S.A., Hofstadler, S.A., and Griffey R.H. (2002) SAR by MS a ligand based technique for drug lead discovery against structured RN A targets. 

Many types of modeling techniques are available in the discovery phase of drug development, from structure activity relationships (SAR) to physiology based pharmacokinetics (PBPK) and pharmacokinetics-/pharmacodynamics (PK/PD) to help choosing some of the lead compounds. Some tests that are carried out by discovery include techniques related to structure determination, metabolism, and permeability NMR, MS/MS, elemental analysis, PAMPA, CACO-2, and in vitro metabolic stability. Although they are important as a part of physicochemical molecular characterization under the biopharmaceutics umbrella, they will not be discussed here. The reader can find relevant information in numerous monographs [9,10]. 

All relevant information on suspected unexpected serious adverse reactions (SARs) considered life threatening or fatal must be reported to CA in all MS and to the IEC as soon as possible or within 7 days of the sponsor learning of them and all follow-up information within a further 8 days. All other reactions are to be advised within 15 days of knowledge by the sponsor. Member States are responsible for recording all SARs and sponsors for advising all investigators. 

Now we investigate the symplectin active site by using a photoaffinity labeling and the nano-LC-Q-TOF-MS analysis and also study the structure and activity relationship (SAR) between DCT structures and symplectin bioluminescent activities. For the SAR study, we also developed a novel synthetic method for DCT analogs. ... 

The NOSV gives a better estimate of the detectability of marine oil pollution, independently of the local wind conditions of this particular study. These results show that higher wind speeds cause lower detectability of oil pollution, and the maximum (model) wind speed where oil spill detection in European coastal waters can be inferred. In particular, at wind speeds below 7 m s 1 oil spills are well detectable, whereas above 10 m s 1 wind speed the definite detection of marine oil pollution seems to be almost impossible. At wind speeds between 7 and 10 m s 1 the detectability of oil spills is rather low. These results can explain why less oil pollution was detected in the northern test areas during winter time. E.g., the mean wind speed in the central North Sea during winter time lies above 10 ms"1 (Figure 5), thus making it unlikely that every oil spill in that area was detectable by SAR sensors. 

The cyclonic eddy-like structures, similar to eddies 10 and 15 (Figure la) and 9-11 (Figure 4), are typical of the Kuroshio Current area east of Taiwan. They have been detected on many ERS-1/2 SAR images however, their position is variable. These eddies were observed due to their radar contrast against the background and/or the presence of definite structures (narrow spiral lines), resulting from the modulation of surface roughness by variable currents. Filamentary slicks were much less common here to favour their detection. Estimates of the current velocity for two eddies obtained by the analysis of the oil spill displacements were found to be 0.07-0.08 ms"1 and 0.3 ms"1. 

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