Chemical tag

Fig. 13.2. Use of chemical tags to encode the sequence in a combinatorial synthesis on a solid support. Reproduced from W. C. Still, Acc. Chem. Res., 29, 155 (1996), by permission of the American Chemical Society.

The abundance patterns of individual stars of different ages and environments enable us to unlock the evolutionary history of galaxies. Many physical characteristics of a galaxy may change over time, such as shape and colour, however the metal content and abundance ratios of stellar atmospheres are not so easy to tamper with. Stars retain the chemical imprint of the interstellar gas out of which they formed, and metals can only increase with time. This method to study galaxy evolution has been elegantly named Chemical Tagging [2],... 

Leitner, A., and Lindner, W. (2004) Current chemical tagging strategies for proteome analysis by mass spectrometry./. Chrom. B813, 1-26. 

In addition to the stable isotope labeling ( 0 versus 0) of proteins for quantifiable proteomic analyses as described above, chemical approaches to the protein-labeUng problem have developed in great variety. These so-called affinity tags can be used to label specific side chain groups such as sulfhydryl or amino groups, active sites for serine and cysteine hydrolases and many others. This active research area has been reviewed recently by A. Leitner and W. Lindner in a Proteomics article entitled Chemistry meets proteomics The use of chemical tagging reactions for MS-based proteomics. ... 

Scheme 13.57. Use of Chemical Tags to Encode Sequence in Combinatorial Synthesis on Solid...

The DNA, the primer, and the four bases are placed in four test tubes. The primer is chemically tagged with dye. Then, a chemically modified version of one base—A, T, C, or G—is added to each test tube. The reaction is started with the addition of DNA polymerase. In each tube, sets of DNA strands, complementary to the DNA to be sequenced, are made. Synthesis of a strand stops when, at random, the modified form of the base is added. There are millions of copies of the DNA to be sequenced in each tube, and at the end of an hour or so, there are millions of copies of strands, each stopped... 

Phosphorylation on serine, threonine, and tyrosine residues is an extremely important modulator of protein function. Phosphorylation can be analyzed by mass spectrometry with enrichment of compounds of interest using immobilized metal affinity chromatography and chemical tagging techniques, detection of phosphopep-tides using mass mapping and precursor ion scans, localization of phosphorylation sites by peptide sequencing, and quantitation of phosphorylation by the introduction of mass tags (McLachlin and Chait 2001). 

Poorly reactive (poorly sequestrable) byproducts are more frequently encountered than poorly sequestrable reactants. A few reports have appeared describing the use of soluble bifunctional linking reagents to chemically tag... 

Polymer-assisted solution-phase synthesis offers strategies for chemical library construction that complement solid-phase methods. Tools now available include chemoselective sequestering resins, bifunctional solution-phase linking reagents, bifunctional chemically tagged reagents, and an... 

Parlow, J. J. Naing, W. South, M. S. Flynn, D. L. In Situ Chemical Tagging Tetrafluorophthalic Anhydride as a Sequestration Enabling Reagent (SER) in the Purification of Solution-Phase Combinatorial Libraries, Tetrahedron Lett. 1997, 38, 7959. 

Starkey, G. W. Parlow, J. J. Flynn, D. L. Chemically-Tagged Mitsunobu Reagents for Use in Solution-Phase Chemical Library Synthesis, Bioorg. Med. Chem Lett. 1998, 8, 2385. 

Sequential chemical tagging methods uses specific compounds (tags) as a code for the individual steps in the synthesis. These tag compounds are sequentially attached in the form of a polymer-like molecule to the same linker or bead as the library compound at each step in the synthesis (Figure 6.10). The amount of tag used at each step must be strictly controlled so that only a very small percentage of the available linker functional groups are occupied by a tag. At the end of the synthesis both the library compound and the tag compound are liberated from the bead. The tag compound must be produced in a sufficient amount to enable it to be decoded to give the history and hence the possible structure of the library compound. 

In a recent experiment, translational and rotational motion of a single molecule was driven and monitored by the STM tip at 7 K in a sort of rack-and-pinion device.67 The pinion consists of a 1.8 nm diameter molecule acting as a six-toothed wheel interlocked at the edge of a self-assembled molecular island functioning as a rack. The rotation of the pinion molecule tooth by tooth along the rack could be monitored owing to the presence of a chemical tag attached to one of its cogs. 

A second paradigm for deconvolution is through libraries based on an encoded bead method (Fig. 6). In this method a readable chemical tag was simultaneously attached to the individual bead for each step in the synthesis of the actual molecule on the bead [66], Herein the library is based on a one-bead-one-compound method, and the activity is measured for individual beads. This determination of activity can be while the test compound is still attached to the bead, where the tag is read directly after the activity is measured. Alternatively, the test compound is cleaved from the bead in a manner that, once activity is detected, allows one to directly return to the individual bead in order to read the tag. The original research in this area was done by Lam and co-workers [14,67, 68], These efforts have progressed to the issuance of a U.S. patent on the one-bead-one-compound methodology with claims for peptide libraries [69], The consequences of the appearance of this patent to those using one-bead-one-compound methods are undetermined at this time. 

For linear multistep syntheses, the split and recombine strategy is a fast and effective method ofproducing large libraries. In fact, a synthesis with x inputs andy chemical steps gives rise to a library of xy components. Chemical tagging methods have been used extensively for the identification of active components in such libraries [6]. An alternative to chemical tagging is a coding system that uses radio frequency (rf) encodable microchips. 

In this technique, an rf encodable microchip is coupled with a capsule of derivatized polystyrene resin such that each unique synthesis site can be tagged with a unique identifier code. The inert nature of the rf transponder construction renders this tagging strategy compatible with virtually all synthetic methods. Additionally, the noninvasive transmission or retrieval of information from any capsule is unambiguous and instantaneous, avoiding the possibility of long reaction and/or analysis times associated with chemical tags. 

The OntoCODE system effectively combines the advantages of both the spatially dispersed and split and recombine strategies and allows the chemist to build large archiv-able combinatorial libraries with milligram quantities of each compound and without the need for chemical tagging. 

A different approach has used a basic tagged ruthenium complex for facile recovery and immobilization using PS-S03H [161,162]. A chemically tagged catalyst was immobilized to the solid phase (37), and the catalyst was activated because of the ammonium ion s electron-withdrawing properties (Scheme 4.74). The catalyst was used for ring closing metathesis in a continuously recirculated system (5 mol% Ru)... 

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