Screening protocols

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

Good A. Structure-based virtual screening protocols. Curr Opin Drug Discov Dev 2001 4 301-7. 

Fig. 9 High-throughput screening protocol for the chain shuttling screen...

As more and more enzymes become available, it is essential to develop an automated microtiter-based screening protocol, which allows the rapid identification of desired biocatalyst hits from a family of enzyme libraries using a minimal amount of substrates and enzymes. As a result of comprehensive screening, the success rate can be significantly improved and many unique enzymes or conditions can be identified, which were previously largely ignored in the synthetic community (Yazbeck et al. 2003). 

Fig. 36.6 Phosphoramidite library synthesis and screening protocol. (Reproduced by permission of the American Chemical Society from [36].)...

Evers, A., Hessler, G., Matter, H. and Klabunde, T. (2005) Virtual screening of biogenic amine-binding G-protein coupled receptors comparative evaluation of protein- and ligand-based virtual screening protocols. 

These three simple observations (time, substrate and NADPH dependence) can be used to detect potential MBIs early in the dmg discovery process, as simple experiments can be designed from established screening protocols used to measure CYP... 

Smith, R., Hubbard, R.E., Gschwend, D.A., Leach, A.R., and Good, A.C. Analysis and optimization of stmcture-based virtual screening protocols (3). New methods and old problems in scoring function design. 

The GPC spin column/ESI-MS screening protocol rapidly analyzes the ability of small organic molecules to bind non-covalently to target protein molecules. 

Despite the fact that solvent effects on enzyme enantioselectivity appear to resist our efforts to rationalize their outcome using commonly accepted solvent descriptors, the effects are certainly there. An impressive example is provided in a report on the successful resolution of ds/trans-( 1 R,5 R)-bicyclo[3.2.0]hept-6-ylidene-acetate ethyl esters, intermediates in the synthesis of GABA (y-aminobutyric acid) analogs, by the Pfizer Bio transformations and Global R D groups (Scheme 2.2) [136]. From a screening protocol, CaLB was identified as a reactive catalyst for the hydrolysis of the racemic mixture of / //-os lor enantiomers with approximately equal activity for the ds- and tmns-isomers and a rather modest (E = 2.7) preference for the /Z-(lR,5R)-enantiomers. Application of medium engineering resulted in a phenomenal increase in the enantioselectivity (addition of 40% acetone, E > 200), while the ds- and trans-isomers were still converted at an almost equal rate. 

Many aspects of this design strategy have been presented. A screening protocol... 

Rogers, J.A., Tedaldi, D.J. Kavanaugh, M. C. (1993). A screening protocol for bioremediation of contaminated soil. Environmental Progress, 12, 146-56. 

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