Spectrometric Encoding

All chemical tagging strategies are greatly limited by the additional synthetic transformations required to build up not only the product but also the tag. Consequently, this encoding method is only used exceptionally for the production of libraries [15-17]. 

Chemical encoding strategies rely on the assumption that the chemical analysis of a given member of the library is more difficult than the analysis of a chemical tag. In most cases this assumption is valid and justifies the described technique. Some libraries have been prepared and characterized by individual mass spectrometric analysis of each member of the library. However, to obtain unambiguous results, the following criteria must be fulfilled  

Each member of the library must have a different molecular weight. 

The compounds must ionize without destruction in the gas phase. 

These requirements seem to be rather limiting, but a synthetic linker to a solid support was recently described which enhances ejection of the product upon laser 

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Due to the aforementioned limiting factors, spectrometric encoding is not broadly applicable and is used only rarely for the encoding of libraries. 

Fitch et al. has recently published a new cation-exchange LC/MS method for decoding dialkylamine-encoded combinatorial libraries without the necessity to derivatise [35] and using a new tag set designed to contain unique masses for each code. We have concentrated on the development of new chromatographic and mass spectrometric methods that utilise the rapid dansyl derivatisation to improve specificity as well as chromatographic reproducibility and resolution. 

The human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATE) and HTLV-l-associated myelopathy/tropical spastic paraparesis (HAM/ TSP) [69]. HTLV-1 encodes a transactivator. Tax, that is critical for virus replication and plays a central role in the development of ATL and HAM/TSP [69]. Tax does not bind to DNA directly but functions by interacting with a variety of cellular proteins [69]. Many protein-protein interactions of Tax have been determined by mutational analysis including CREB [70-72] and NF-kB [70,72]. To identify all the cellular proteins that interact with Tax, Wu et al. used chromatography, 2D gel electrophoresis, and mass spectrometric analysis of an HTLV-1-infected cell line (C81) [73]. As Tax functions in both the cytoplasm and the nucleus [70,74], Tax-interacting proteins were identified from both cellular compartments. Some of the cytoplasmic proteins included small GTPases and components of the cytoskeleton while some of the more interesting nuclear proteins included components of the SWl/SNF chromatin remodeling complex [73]. 

A database may consist of a simple look-up table relating two variables, such as solvent composition and polarity, tables of statistical factors for tests of significance (Q, F and t-tests), or archived sample data and analytical procedures. Larger compilations of data may list chemical formulae and structures or characteristic properties of elements, compounds, materials and commercial formulations (e.g., boiling point, viscosity, dielectric constant, hardness and toxicity). Spectrometric and chromatographic analytical databases are of particular value in the characterization and identification of unknown substances, and some examples are given in Table 1. The data is usually compressed and encoded to maximize the amount of information that can be stored. 

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