Screening of combinatorial libraries

Q Zheng, DJ Kyle. Computational screening of combinatorial libraries. Bioorg Med Chem 4(5) 631-638, 1996. 

The data show that SSIMS can be used as a tool for characterizing the different steps in the production of biosensors, or even for sequencing. Similarly, SSIMS can be used to solve a variety of problems in bioanalytical chemistry, e. g. screening of combinatorial libraries, characterizing Langmuir-Blodgett layers, etc. 

Shin YG, van Breemen RB Analysis and screening of combinatorial libraries using mass spectrometry. Biopharm Drug Dispos 2001, 22, 353-372. 

ESI-MS has been used for the quantification of a number of substrates and products of enzymatic reactions [56,57]. Hsieh et al. report the use of ion spray mass spectrometry (a technical variation of electrospray ionization) coupled to HPLC for the kinetic analysis of enzymatic reactions in real time [58]. The hydrolysis of dinucleotides with bovine pancreatic ribonuclease A and the hydrolysis of lactose with 3-galactosidase were monitored and the resulting data were used for the estimation of and v x of these reactions. Another field of application of electrospray mass spectrometry is the screening of combinatorial libraries for potent inhibitors [31,59]. 

D., Wang, . C. (2001) Virtual screening of combinatorial libraries across a gene family in search of inhibitors of Giardia lamblia guanine phosphoribosyltransferase. Antimi-crob Agents Chemother 45, 2571-2576. 

Moates, F.C., et ah, Infrared thermographic screening of combinatorial libraries of heterogeneous catalysts. 

The feasibility of FTICR-based approaches for the screening of combinatorial libraries was demonstrated using flow injection (Fang... 

Georgiou, G., Stathopoulus, C., Daugherty, P. S., Nayak, A. R., Iverson, B. L., and Curtiss III, R. (1997). Display of heterologous proteins on the surface of microorganisms from the screening of combinatorial libraries to live recombinant vaccines. Nature Biotechnology, 15, 29-34. 

In this chapter we will discuss not only the methods and techniques used for analysis of small-organic-molecule libraries but also the approaches for generation of these libraries, with the understanding that synthesis, analysis, and screening of combinatorial libraries are the integrated parts of combinatorial technology. 

Beroza P, Bradley EK, Eksterowicz JE, Feinstein R, Greene J, Grootenhuis PDJ, Henne RM, Mount J, Shirley WA, Smellie A, Stanton RV and Spellmeyer DC, Applications of random sampling to virtual screening of combinatorial libraries, /. Mol. Graphics Modelling, 18 335-342, 2000. 

In this way HTS allows the rapid screening of combinatorial libraries for potential lead compounds. These lead compounds are then isolated and characterized, if necessary, before production and optimization on a larger scale. 

Zotchev SB, Stepanchikova AV, Sergeyko AP, Sobolev BN, Filimonov DA, Poroikov VV (2006) Rational Design of Macrolides by Virtual Screening of Combinatorial Libraries Generated Through in silico Manipulation of Polyketide Synthases. J Med Chem 49 2077... 

To assess the quality of a combinatorial chemistry library, it is essential to determine the purity and quantity of the expected products. Commercial software, developed by instrument manufacturers, has made possible the unattended and rapid analysis of tens of thousands of individual components of a specific library. The application of LC/MS in high-throughput screening of combinatorial libraries has been reviewed by several authors [72-78]. 

In Fig. 7 a few representative examples of molecular probes identified by screening of combinatorial libraries are depicted. 

Sandman KE, Tardiff DF, Neely LA, Noren CJ. Revised Escherichia coli selenocysteine insertion requirements determined by in vivo screening of combinatorial libraries of SECIS variants. Nucleic Acids Res. 2003 31 2234-2241. 

APPl has now found its place in LC-MS, next to ESI and APCl. Commercial APPl sources are available and apphed in various application areas [64-65], Dnal APCl/APPl and ESl/APPl provide extended applicability range of LC-MS, which is especially nseful in screening of combinatorial libraries and other studies in early drag discovery [63, 75], Another attractive feature of APPl, which so far has only been explored in the coupling of capillary electromigration techniques with MS [76-77], is that it apparently is less disturbed by the presence of phosphate buffers and srrrfactants. 

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