Carbohydrate libraries, solid-phase synthesis

Other known oligonucleotide analogs include oligomers in which the heterocyclic bases have been modified [155] or replaced by other types of compound [156], Solid-phase syntheses of hybrids of DNA with peptides [157-163], with carbohydrates [164,165], and with PNA (peptide nucleic acids, see Section 16.4.1.2 [166-168]) have also been reported, and several strategies have been developed that enable the preparation of oligonucleotides with a modified 5 - or 3 -terminus [169-174] or of cyclic oligonucleotides [122,175], Various techniques for the parallel solid-phase synthesis of oligonucleotides have been developed for the preparation of compound libraries [176-181],... 

Based on a library-directed approach, Takahashi and co-workers developed a synthetic strategy for the combinatorial solid-phase synthesis of tree-type carbohydrate clusters using three types... 

Synsorb. Because several of these supports are also used in solid-phase synthesis, an advantage of using carbohydrate-displaying beads as model systems for polyvalent recognition events is that libraries of saccharides can be assembled. Therefore, structure-function relationships can be determined rapidly. 

Automated solid phase synthesis, which has enabled synthesis libraries of peptides (15) and nucleic acids (16) and their use in drug discovery, is emerging as a useful tool for carbohydrate production (17). This technology has been difficult to develop largely due to the aforementioned inherent complexity of carbohydrates (18). Both nucleic acids and proteins can be assembled only in head-to-tail chains, whereas a chain of carbohydrates has the potential to elongate at any one of five different points on the sugar and these linkages can... 

There have been several recent solid-phase and solution-phase libraries reported that contain the spiroketal moiety (Figure 7.5). These libraries introduce additional structural complexity and new interaction modes of carbohydrate-like molecules with biological targets. Ley and cowoikers reported the solid-supported synthesis of spiroketals. Using stereoselective aldol reactions of boron enolates, the Waldmann and Paterson groups reported the solid-phase synthesis of 6,6-spiioketals. The 1,7-dioxaspiro [5.5]undecane spiroketal served as the core template for Porco s three-point diversity library to explore protein-protein interactions. ... 

Merrifield s revolutionary concept of solid-phase synthesis was not limited to peptides, and similar techniques have been developed for the synthesis of nucleic acids and carbohydrates on solid supports. For each application, specialized instrumentation that is computer-controlled is commercially available. Access to such equipment has enabled researchers in areas of biology, medicine, material science, and biomedical engineering to prepare thousands of peptides and polypeptides for study. In the pharmaceutical industry, for example, solid-phase synthesis has been used to prepare relatively large numbers of related molecules, so-called compound libraries, that... 

Automated carbohydrate synthesis allows for the production of complex carbohydrates orders of magnitude faster than other approaches. This advance has the potential to parallel the breakthroughs achieved by researchers in the peptide and DNA fields that opened up the pro-teomic and genomic eras in biotechnology. By increasing the scope of the carbohydrate building block library and streamlining the reaction conditions further we anticipate that automated solid-phase carbohydrate synthesis will become the method of choice for carbohydrate production. 

Liang R, Yan L, Loebach J, Ge M, Uozumi Y, Sekanina K, Horan N, Gildersleeve J, Thompson C, Smith A, Biswas K, Still WC, Kahne D, Parallel synthesis and screening of a solid phase carbohydrate library, Science, 274 1520-1522, 1996. 

Another important discovery in the area of combinatorial synthesis with di- and tri-saccharides was made by Kahne and co-workers at Princeton [4c]. Kahne s approach utilized solid phase technology to synthesize a saccharide library (Scheme 3), which was especially challenging since, in order for a solid phase approach to be successful, bonds between monomers must be formed in high yields. This is not trivial since most high-yielding coupling reactions in carbohydrate chemistry are not general in nature [5]. 

Seeberger PH, Haase WC. Solid-phase oligosaccharide synthesis and combinatorial carbohydrate libraries. Chem. Rev. 2000 100 4349-4394. 

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