Supports for Solid-Phase Libraries

For the solid-phase synthesis of glycopeptides, both polystyrene and PEG-based resins have been successfully used. Experiments that compare the rates of reactions on various resins have revealed that the rate of reaction completely depends on the nature of the reaction itself 45 Some reactions perform better on hydrophobic resins, while others are better on hydrophilic resins. 

As of this writing, there are presently only two examples of successful synthesis of glycopeptide libraries in the literature, and these have been generated using PEG-based resins (PEGA and POEPOP), thus enabling rapid solid phase screening of the library (see Sections 14.8 and 14.7.2). 

Polystyrene-based resins have been used successfully for the solid-phase synthesis of glycopeptides and oligosaccharides. Experiments that compare the rates of a reaction on a PS-resin compared to TentaGel have revealed that the rate of reaction completely depends on the nature of the reaction itself [36], Some reactions perform better on hydro-phobic resins, while others are better on hydrophilic resins. Another issue of particular importance for the synthesis of oligosaccharides on solid phase is the influence of the solid support on the stereochemical outcome of the reaction. There are few detailed studies that address this issue however, preliminary results are contradictory, but indicate that as in solution-phase reactions, the anomeric ratio is strongly influenced by the solvent, C-2 group on the donor and temperature [37-39]. In some cases there seems to be an enhancement of anomer selectivity on the solid phase [38]. 

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M. Winter, Support for solid-phase organic synthesis, in G. Jung, (Ed.), Combinatorial Peptide and Nonpeptide Libraries, VCH, Weinheim, 1996, pp. 465-510. 

Barany, G., Alberido, F., Kates, S.A. and Kempe, M. (1997) Polyethylene glycol)-Containing Supports for Solid-Phase Synthesis of Peptides and Combinatorial Organic Libraries. In ACS Symposium Series 680. Polyethylene glycol) Chemistry and Biological Applications (eds J.M. Harris and S. Zalipsky), American Chemical Sodety, Washington, DC, pp. 239-64. 

During their evalnations, plugs were used as supports for solid-phase synthesis of small libraries of biaryl compounds, sulfonamides, tertiary amines, ureas, and amides. Althongh yields and purities were similar to the loose beads counterpart, the reaction times were slightly increased. Becanse of their mechanical stability and limited swelling, plugs are much easier to handle than the corresponding... 

Combinatorial chemistry has moved from specially centralized laboratories, often equipped with multimillion-dollar robots, onto the bench of individual medicinal chemists. This change in direction requires the availability of personal chemistry tools that are simple to operate, easy to arrange in the laboratory, and reasonably priced. Such instruments are now available for the effective synthesis of combinatorial libraries. The Encore synthesizer represents a simple and efficient personal chemistry tool that allows the execution of directed split-and-pool combinatorial synthesis. The current version of the Encore synthesizer is designed for solid-phase synthesis on SynPhase Lanterns however, it can be modified for synthesis on alternative solid supports such as resin plugs from Polymer Laboratories (e.g., StratoSpheres Plugs). 

Cyclic disulfide libraries have primarily been generated through sohd-phase oxidation of support-bound peptide libraries, either on resin beads l or on a cellulose membrane support.P A study comparing several methods for solid-phase and solution cyclizationt found oxidation with hydrogen peroxide (1.5 equiv at a peptide concentration of 0.5g L i) to be best suited for the generation of cyclic disulfide peptide hbraries in solution. 

The development of a support/linker system for the microwave-assisted synthesis of dihydropyrimidine test libraries, and methods for solid-phase scale-up on cellulose were recently described [101]. 

To avoid the possibility that a small peptide from a phage-displayed library will not bind adequately when immobilized on a solid support, Baumbach and Hammond suggested that combinatorial peptide libraries for protein purification be synthesized directly on resins that could be used as chromatographic supports on a large scaled, in this way, any ligand that is identified is already on a platform or format that would facilitate implementation in downstream processing. The one-bead-one-peptide solid phase library format is ideally suited for this purpose, if the library is built on chromatographic resins that can withstand the harsh solvent conditions used for peptide synthesis. 

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