Tandem sequences advantages

The major advantage of the tandem mass spectrometry approach compared to MALDI peptide fingerprinting, is that the sequence information obtained from the peptides is more specific for the identification of a protein than simply determining the mass of the peptides. This permits a search of expressed sequence tag nucleotide databases to discover new human genes based upon identification of the protein. This is a useful approach because, by definition, the genes identified actually express a protein. 

The second approach is the tandem mass spectrometric method (Wilm et ah, 1996 Link et ah, 1999 Yates, 2000). This method relies on fragmentation of individual peptides in the tryptic peptide mixture to gain sequence information. Its main advantage is that sequence information derived from several peptides is much more specific for the identification of a protein than a list of peptide masses. The sequence data can be used to search not only protein sequence databases but also nucleotide databases such as expressed sequence tag (EST) databases and, more recently, even... 

Pyrrolidines are an important class of five-membered heterocycles with noteworthy biological properties [46]. In addition to pharmaceutical applications, the pyrrolidine moiety has also been widely used as a chiral auxiliary for asymmetric synthesis [47]. Although many elegant syntheses of chiral nonracemic pyrrolidines have been reported within the past decade or so [48-50], an alternative approach based on the intramolecular reaction of an azide and organoborane has been developed very recently [51-53], This approach utilizes the hydroboration-azide alkylation tandem reaction as a key sequence, taking advantage of the efficient stereocon-trolled steps. Scheme 20 shows an application of the synthesis of 3-substituted 5-(2-pyrrolidinyl)isoxazole which has been found to have nanomolar activity, comparable to (5)-nicotine, against whole rat brain [54]. 

The use of organolithium intermediates in tandem synthetic sequences combines the versatility of the very well known organolithium reagents and their highly stereoselective chemistry, with the economic and environmentally friendly advantages of the one-pot and/or cascade strategy, when compared with the conventional stepwise synthetic pathways. 

One of the important advantages of a tandem accelerator is that apparently does not form negative ions that live long enough to pass through the accelerator to the terminal (18,31). Thus a primary source of background is essentially eliminated. Another important characteristic of a TAMS is the fact that it is a relatively simple operation to sequence the acceleration of the various isotopes of carbon through the system in a reproducible manner. Thus measurements can be made of and... 

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