Progress in Primary Structure Analysis

Notable progress in the structural analysis of methylene derivatives of the polyhydric alcohols resulted from the investigations of Hann, Hudson and their co-workers26 80,40-4 into the behavior of these compounds during acetolysis. It was found that a mixture of acetic anhydride, acetic acid and 1-2% sulfuric acid ruptures preferentially any methylene bridge which spans a primary and a secondary position, giving the acetate ester of the primary hydroxyl and the acetoxymethyl ether of the secondary hydroxyl subsequent treatment with sodium methoxide removes each of these substituents. Under similar conditions, the acetolysis of a benzylidene compound results in the replacement of the arylidene residue, wherever it is located in the molecule, by two acetyl groups.16 29 47 48... 

Recent progress in electron diffraction has significantly broadened its applications from a primary a microstructure characterization tool to an accurate structure analysis technique that traditionally belongs almost exclusively to the domain of X-ray and neutron diffraction. This development is timely since the focus of modem materials feature size is increasingly on nanoscale stmctures, where the electron high spatial... 

In 1944, about the time Sanger determined the primary structure of insulin, two-dimensional paper chromatography became available for analyzing amino acids of protein samples.32 This method allowed Sanger to analyze 20 amino acids in a single run with considerably less sample and time compared to the previous methods. The development of an automated amino acid analyzer in 1958 by Spackman, Stein and Moore had made further progress.33 This first amino acid analyzer performed an analysis with 1 pmol of sample in 20 hours. Due to the continuous improvements made on amino acid analyzers,... 

An important factor in the progress of bioinformatics has been the constant increase in computer speed and memory capacity of desktop computers and the increasing sophistication of data processing techniques. The computation power of common personal computers has increased within 12 years approximately 100-fold in processor speed, 250-fold in RAM memory space and 500-fold or more in hard disk space, while the price has nearly halved. This enables acquisition, transformation, visuahsation and interpretation of large amounts of data at a fraction of the cost compared to 12 years ago. Presently, bioanalytical databases are also growing quickly in size and many databases are directly accessible via the Internet One of the first chemical databases to be placed on the Internet was the Brookha-ven protein data bank, which contains very valuable three-dimensional structural data of proteins. The primary resource for proteomics is the ExPASy (Expert Protein Analysis System) database, which is dedicated to the analysis of protein sequences and structures and contains a rapidly growing index of 2D-gel electrophoresis maps. Some primary biomolecular database resources compiled from spectroscopic data are given in Tab. 14.1. 

Nevertheless, the primary tool used in solution-phase synthesis for structural elucidation is NMR spectroscopy. There has been some interest in developing NMR methods for analyzing resin-bound compounds and monitoring the progress of chemical reactions on solid-phase by on-bead analysis (without cleavage of the product from the resin). Many improvements have been achieved in NMR for SPS, but hmitations remain. On the one hand, the limited mobility of polymers, as well as the poor mobility of attached compounds, leads to broad bands with low spectral resolution. On the other hand, the broad signals due to the polymer matrix can mask or overlay with bands from the desired product. The main advantage of this technique is its nondestructive nature, as the sample can be easUy recovered. The next section will focus on the most powerful technique developed to monitor and characterize polymer-supported compounds gel-phase HR-MAS NMR spectroscopy. 

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