Library analysis techniques

Barnard, J.M., Downs, G.M., ScHOLLEY-PFAB, A.V., and Brown, R. D. Use of Markush structure analysis techniques for descriptor generation and clustering of large combinatorial libraries./. Mol. Graph. 2000, 38, 452-463. 

There are, however, situations where classic strategies of thermodynamically controlled screening are difficult to apply. Many times, the complex libraries are difficult to analyze in spite of the progress in analysis techniques and instrumentation. Isolation of the amplified products is also... 

Key words Virtual combinatorial library, Markush technique, compound analysis, chemoinfor-... 

These same analysis techniques can be applied to chemical imaging data. Additionally, because of the huge number of spectra contained within a chemical imaging data set, and the power of statistical sampling, the PLS algorithm can also be applied in what is called classification mode. In this case, the reference library used to establish the PLS model is... 

The first method used a similarity metric to select the top percentage of hits and the second method does the selection based only on number of common pharmacophores between the receptor active site fingerprint and the 3D fingerprint for compounds in the virtual library. Both analysis techniques are extremely fast. One of the major advantages of FLIP technology is its throughput. 

As the preparation of large libraries for lead discovery became routine, the burden placed on analysis techniques focused mainly on throughput and qual-ity. ° However, biological assay requirements typically required pure compounds. Thus, the focus shifted toward the use of automated high throughput purification methods applied to libraries of discrete compounds. Reverse-phase analytical and preparative HPLC formats in conjunction with MS techniques have been critical for the high throughput purification... 

R678 K. Nokihara, Recent Progress in Combinatorial Chemistry. Combinatorial Analysis for Assaying Library. Hyphenated Techniques , Kagaku to Seibutsu, 2001,39, 56... 

For library analysis of compound mixtures, reliable results are obtained by coupling mass spectrometry with HPLC or capillary electrophoresis (CE). In this arrangement, mixtures of several hundred compounds can be analyzed. A comparison of MS, CE, and NMR for library characterization has been made in [93]. It was concluded that existing analytical techniques can provide sufficient information about prepared libraries. 

An additional dimension to library analysis is introduced when mass spectrometry is coupled with common separation techniques, for example liquid chromatography (LC) and capillary electrophoresis (CE). While these couplings are compatible with spray ionization techniques such as ESI or APCI, they more or less exclude the use of the MALDI technique. Several contributions deal with LC-ES-MS [36, 37] and CE-ES-MS-coupling [38], For molecules with isobaric nominal masses, MS/MS-experiments are performed to confirm the identity of a library component. Separation and analysis of compound mixtures may also be performed by GC-MS [39, 40], As a supplement to the more common-... 

Library analysis becomes more complicated when the formation of stereo- or regio-isomers is possible, as the size of the library is increased by the number of possible isomers. In order to allow a rapid and uncomplicated evaluation, it is therefore important to design the library before synthesis such that the library size is restricted to a maximum of 15 to 20 possible compounds. It must be stressed that the MS investigations presented here have not fully explored the potency of either the mass spectrometric or the chromatographic techniques. The authors are conscious of the wealth of other experiments and possibilities to analyze fully a specific combinatorial library with optimized analytical techniques. Therefore, it is important to realize that in library analysis, compromises have to be made according to the priority of full sample characterization or high throughput. 

HIGH-THROUGHPUT NMR TECHNIQUES FOR COMBINATORIAL CHEMICAL LIBRARY ANALYSIS... 

LL High-Throughput Analytical Techniques for Comhinatorial Library Analysis... 

In the field of proteomics, arrays can also be used to identify possible interaction partners. Here, the array is spotted with recombinant proteins or antibodies and then hybridised with labelled cell lysate or an expressed cDNA library. Additionally, techniques like two-dimensional gel electrophoresis, the identification of isolated proteins by mass spectrometry or the two-hybrid analysis are valuable tools to identify new proteins. These methods allow a large-scale study of viral and cellular proteins without knowledge of the DNA sequence (Fig. 1, IV. For review, see Pandey and Mann 2000). 

T. Hou and D. Raftery, High-Throughput NMR Techniques for Combinatorial Chemical Library Analysis , Chem.Anal., 2004,163,139... 

---