Combinatorial approaches, chemical synthesis

High selectivity and substrate specificity of glycosyl transferases make them valuable catalysts for special linkages in polymer-supported synthesis. There is, however, still a rather limited set of enzymes available to date, and the need to synthesize a variety of natural and non-natural oligosaccharides prevails. Particularly with regard to combinatorial approaches, chemical solid-phase oligosaccharide synthesis promises to meet the demands most effectively. 

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

Miniaturization and parallelization key approaches for drug development apparatus for combinatorial chemistry UHTS 1536 titer-plate format modular construction of apparatus applications of UHTS fine-chemical synthesis by micro reactors numbering-up nature as model general advantages of micro flow vision of plants-on-a-desk [233]. 

Because the chemical structure of a molecule encodes its biological properties, structure has long served as the primary variable and determinant for the discovery of new drugs by medicinal chemists. For this reason, systematic structural modification has been the primary tool of choice to isolate and enhance a desired biologic activity. Moreover, with the relatively recent development of in vitro receptor-binding assays, combinatorial methods of chemical synthesis, and computer graphics, the overall approach to structural modification has become increasingly sophisticated. 

There are many variations of combinatorial chemistry, and all have distinct advantages and disadvantages. A comprehensive description of the different techniques is beyond the scope of this chapter. In the following sections, a few examples will highlight the main features common to most combinatorial approaches to library synthesis. This section contains a considerable amount of synthetic chemistry. The goal of this section is not to teach organic synthesis but instead to demonstrate the basics of chemical library synthesis. Do not get lost in the synthesis Focus instead on the characteristics and qualities specific to each combinatorial technique. 

Soluble supports for solution-phase combinatorial synthesis were extensively covered in Section 8.5. A recent survey of available soluble supports, with respect to their use in the soluble supported synthesis of various classes of chemicals (90), highlights the wide range of physicochemical properties (especially regarding solubility, tendency to crystallize, and solubilization power) that are embedded in different polymers and copolymers. The assessment of a sort of S AR for the composition of copol5miers versus their physicochemical properties would require the preparation of a large number of examples. Combinatorial approaches to soluble support libraries could be highly beneficial in this perspective. 

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